Refine
Has Fulltext
- yes (33)
Is part of the Bibliography
- yes (33)
Year of publication
Document Type
- Journal article (33)
Keywords
- black holes (3)
- depression (3)
- expression (3)
- accretion (2)
- association (2)
- consortium (2)
- general relativity (2)
- identification (2)
- microbiome (2)
- onset (2)
Author
- Andrulis, Irene L. (5)
- Couch, Fergus J. (5)
- Easton, Douglas F. (5)
- Goldgar, David E. (5)
- Hamann, Ute (5)
- Jakubowska, Anna (5)
- Meindl, Alfons (5)
- Mulligan, Anna Marie (5)
- Neuhausen, Susan L. (5)
- Nevanlinna, Heli (5)
- Olopade, Olufunmilayo I. (5)
- Radice, Paolo (5)
- Terry, Mary Beth (5)
- Aittomäki, Kristiina (4)
- Antoniou, Antonis C. (4)
- Barrowdale, Daniel (4)
- Benitez, Javier (4)
- Caligo, Maria A. (4)
- Chenevix-Trench, Georgia (4)
- Daly, Mary B. (4)
- Dennis, Joe (4)
- Devilee, Peter (4)
- Diez, Orland (4)
- Ejlertsen, Bent (4)
- Engel, Christoph (4)
- Evans, D. Gareth (4)
- Frost, Debra (4)
- Garber, Judy (4)
- Glendon, Gord (4)
- Greene, Mark H. (4)
- Hogervorst, Frans B. L. (4)
- Imyanitov, Evgeny N. (4)
- Janavicius, Ramunas (4)
- John, Esther M. (4)
- Manoukian, Siranoush (4)
- McGuffog, Lesley (4)
- Nathanson, Katherine L. (4)
- Offit, Kenneth (4)
- Olah, Edith (4)
- Osorio, Ana (4)
- Pedersen, Inge Sokilde (4)
- Peterlongo, Paolo (4)
- Rennert, Gad (4)
- Singer, Christian F. (4)
- Thomassen, Mads (4)
- Tung, Nadine (4)
- Vijai, Joseph (4)
- Weitzel, Jeffrey N. (4)
- Adlard, Julian (3)
- Arnold, Norbert (3)
- Arun, Banu K. (3)
- Balmaña, Judith (3)
- Blackburn, Lindy (3)
- Bonanni, Bernardo (3)
- Buys, Saundra S. (3)
- Caldes, Trinidad (3)
- Chatterjee, Koushik (3)
- Chung, Wendy K. (3)
- Ding, Yuan Chun (3)
- Doeleman, Sheperd S. (3)
- Domchek, Susan M. (3)
- Eccles, Diana M. (3)
- Einsele, Hermann (3)
- Friedman, Eitan (3)
- Gaudet, Mia M. (3)
- Gehrig, Andrea (3)
- Gerdes, Anne-Marie (3)
- Godwin, Andrew K. (3)
- Gronwald, Jacek (3)
- Hall, Per (3)
- Hansen, Thomas V. O. (3)
- Isaacs, Claudine (3)
- Jensen, Uffe Birk (3)
- Johnson, Michael D. (3)
- Karlan, Beth Y. (3)
- Kast, Karin (3)
- Kwong, Ava (3)
- Laitman, Yael (3)
- Lasset, Christine (3)
- Lazaro, Conxi (3)
- Lester, Jenny (3)
- Mai, Phuong L. (3)
- Montagna, Marco (3)
- Niederacher, Dieter (3)
- Nielsen, Finn C. (3)
- Nussbaum, Robert L. (3)
- Ottini, Laura (3)
- Papi, Laura (3)
- Pauli, Paul (3)
- Pensotti, Valeria (3)
- Ramus, Susan J. (3)
- Rebbeck, Timothy R. (3)
- Robson, Mark (3)
- Roelofs, Freek (3)
- Schmutzler, Rita K. (3)
- Soucy, Penny (3)
- Southey, Melissa C. (3)
- Spurdle, Amanda B. (3)
- Stoppa-Lyonnet, Dominique (3)
- Sutter, Christian (3)
- Tiede, Paul (3)
- Tischkowitz, Marc (3)
- Toland, Amanda Ewart (3)
- Varesco, Liliana (3)
- Wappenschmidt, Barbara (3)
- Yannoukakos, Drakoulis (3)
- de la Hoya, Miguel (3)
- van den Ouweland, Ans M. W. (3)
- Anton-Culver, Hoda (2)
- Arason, Adalgeir (2)
- Arndt, Volker (2)
- Aronson, Kristan J. (2)
- Arras, Philipp (2)
- Arver, Brita (2)
- Barjhoux, Laure (2)
- Barkardottir, Rosa B. (2)
- Beckmann, Matthias W. (2)
- Behrens, Sabine (2)
- Beilhack, Andreas (2)
- Bermisheva, Marina (2)
- Bignon, Yves-Jean (2)
- Blomqvist, Carl (2)
- Bogdanova, Natalia V. (2)
- Bojesen, Stig E. (2)
- Bolla, Manjeet K. (2)
- Bork, Peer (2)
- Brauch, Hiltrud (2)
- Brede, Christian (2)
- Brenner, Hermann (2)
- Brewer, Carole (2)
- Burwinkel, Barbara (2)
- Bäuerlein, Carina A. (2)
- Campbell, Ian (2)
- Canzian, Federico (2)
- Carter, Jonathan (2)
- Chael, Andrew (2)
- Chang-Claude, Jenny (2)
- Chanock, Stephen J. (2)
- Chopra, Martin (2)
- Christiansen, Hans (2)
- Claes, Kathleen (2)
- Claes, Kathleen B. M. (2)
- Clarke, Christine L. (2)
- Cook, Jackie (2)
- Czene, Kamila (2)
- Damiola, Francesca (2)
- Ditsch, Nina (2)
- Donaldson, Alan (2)
- Dorfling, Cecilia M. (2)
- Douglas, Fiona (2)
- Dunning, Alison M. (2)
- Dwek, Miriam (2)
- Dörk, Thilo (2)
- Eeles, Ros (2)
- Ellis, Steve (2)
- Emami, Razieh (2)
- Eriksson, Mikael (2)
- Falkai, Peter (2)
- Fasching, Peter A. (2)
- Fink-Retter, Anneliese (2)
- Flyger, Henrik (2)
- Foretova, Lenka (2)
- Fromm, Christian (2)
- Fuentes, Antonio (2)
- Gabrielson, Marike (2)
- Gago-Dominguez, Manuela (2)
- Gamazon, Eric R. (2)
- Ganz, Patricia A. (2)
- Gapstur, Susan M. (2)
- García-Closas, Montserrat (2)
- García-Sáenz, José A. (2)
- Giles, Graham G. (2)
- Goldberg, Mark S. (2)
- Guenél, Pascal (2)
- Haimann, Christopher A. (2)
- Healey, Sue (2)
- Hodgson, Shirley (2)
- Hopper, John L. (2)
- Hulick, Peter J. (2)
- Huo, Dezheng (2)
- Izatt, Louise (2)
- Jacobs, Lauren (2)
- James, Paul A. (2)
- Jordán Garrote, Ana-Laura (2)
- Karulin, Alexey Y. (2)
- Khusnutdinova, Elza (2)
- Kim, Sung-Won (2)
- Knollmüller, Jakob (2)
- Konstantopoulou, Irene (2)
- Kosogorov, Nikita (2)
- Kraft, Peter (2)
- Kristensen, Vessela N. (2)
- Kruse, Torben A. (2)
- Kuchenbaecker, Karoline B. (2)
- Lambrechts, Diether (2)
- Leboyer, Marion (2)
- Lee, Andrew (2)
- Lehmann, Paul V. (2)
- Lincoln, Anne (2)
- Lindahl, Greg (2)
- Lindström, Sara (2)
- Loman, Niklas (2)
- Long, Jirong (2)
- Loud, Jennifer T. (2)
- Lubiński, Jan (2)
- Mannermaa, Arto (2)
- Manoochehri, Mehdi (2)
- Margolin, Sara (2)
- Mazoyer, Sylvie (2)
- Meijers-Heijboer, Hanne E. J. (2)
- Menon, Usha (2)
- Milne, Roger L. (2)
- Mitchell, Gillian (2)
- Morrison, Patrick J. (2)
- Müller, Hendrik (2)
- O'Donovan, Claire (2)
- Olsson, Håkan (2)
- Olswold, Curtis (2)
- Oostra, Ben A. (2)
- Orsulic, Sandra (2)
- Pankratz, Vernon S. (2)
- Papp, Janos (2)
- Park-Simon, Tjoung-Won (2)
- Patel, Nimesh (2)
- Peissel, Bernard (2)
- Pfeiler, Georg (2)
- Pharaoh, Paul D. P. (2)
- Phelan, Catherine M. (2)
- Piedmonte, Marion (2)
- Plaseska-Karanfilska, Dijana (2)
- Platte, Radka (2)
- Plendl, Hansjoerg (2)
- Poppe, Bruce (2)
- Preisler-Adams, Sabine (2)
- Presneau, Nadege (2)
- Rantala, Johanna (2)
- Rappaport, Christine (2)
- Raymond, Alexander (2)
- Reif, Andreas (2)
- Rhiem, Kerstin (2)
- Ricarte, Angelo (2)
- Riedel, Simone S. (2)
- Rogers, Mark T. (2)
- Romero, Atocha (2)
- Rookus, Matti A. (2)
- Rosenquist, Richard (2)
- Rouleau, Etienne (2)
- Rouleau, Guy A. (2)
- Saloustros, Emmanouil (2)
- Schlegel, Paul-Gerhardt (2)
- Schmidt, Marjanka K. (2)
- Schmidt, Thomas S. B. (2)
- Senter, Leigha (2)
- Sharma, Priyanka (2)
- Shu, Xiao-Ou (2)
- Side, Lucy E. (2)
- Simard, Jacques (2)
- Simard, Jaques (2)
- Sinilnikova, Olga M. (2)
- Spinelli, John J. (2)
- Steele, Linda (2)
- Steinemann, Doris (2)
- Stone, Jennifer (2)
- Sunagawa, Shinichi (2)
- Sundararaman, Srividya (2)
- Swerdlow, Anthony J. (2)
- Szabo, Csilla I. (2)
- Tapper, William J. (2)
- Tea, Muy-Kheng (2)
- Teixeira, Manuel R. (2)
- Teulé, Alex (2)
- Thull, Darcy L. (2)
- Tihomirova, Laima (2)
- Toland, Amanda E. (2)
- Torres, Diana (2)
- Traianou, Efthalia (2)
- Truong, Thérèse (2)
- Vachon, Celine M. (2)
- Varon-Mateeva, Raymonda (2)
- Vega, Justin (2)
- Viel, Alessandra (2)
- Walitza, Susanne (2)
- Wang, Qin (2)
- Wendt, Camilla (2)
- Wray, Naomi R. (2)
- Zeller, Georg (2)
- Zhang, Wenji (2)
- Zheng, Wei (2)
- Ziogas, Argyrios (2)
- van Leeuwen, Flora E. (2)
- van Rensburg, Elizabeth J. (2)
- Aalfs, Cora M. (1)
- Abboud, Hanna E. (1)
- Abella, Scott R. (1)
- Adelman, Zach N. (1)
- Adler, Sharon G. (1)
- Adli, Mazda (1)
- Adámek, Martin (1)
- Agata, Simona (1)
- Agnarsson, Bjarne A. (1)
- Ahearn, Thomas (1)
- Ahn, Seung-Joon (1)
- Akbar, Umer (1)
- Akiyama, Kazunori (1)
- Aktas, Orhan (1)
- Akula, Nirmala (1)
- Al-Ejeh, Fares (1)
- Alda, Martin (1)
- Alencar, Janderson Batista Rodrigues (1)
- Almeida, Alexandre (1)
- Almeida-e-Silva, Danillo C. (1)
- Altamura, Sandro (1)
- Altenhoff, Adrian (1)
- Alves, Renato (1)
- Alves, Renato J. C. (1)
- Ambrosino, Sara (1)
- Amin, Najaf (1)
- Andersen, Mette K. (1)
- Anderson, Michelle A.E. (1)
- Andreas Conejero, Raquel (1)
- Antrobus, Robin (1)
- Arda, Raffaella (1)
- Arellano-Viera, Estibaliz (1)
- Armisén, David (1)
- Arnold, Paul D. (1)
- Asherson, Philip (1)
- Asseryanis, Ella (1)
- Attardo, Geoffrey M. (1)
- Atzberger, Ann (1)
- Aubry, Jean-Michel (1)
- Augustinsson, Annelie (1)
- Aulchenko, Yurii S. (1)
- Ausems, Magreet G. E. M. (1)
- Azzollini, Jacopo (1)
- BKC, Dukka (1)
- Babbitt, Patricia C. (1)
- Backlund, Lena (1)
- Bacot, Françios (1)
- Bae-Jump, Victoria L. (1)
- Baker, Jeanette (1)
- Banaschewski, Tobias (1)
- Bandeira, Cibele E. (1)
- Bane, Anita (1)
- Bankapur, Asma R. (1)
- Banzato, Claudio E. M. (1)
- Baranov, Alexandr (1)
- Barber, Nicholas A. (1)
- Bardel, Claire (1)
- Bargsten, Joachim W. (1)
- Barile, Monica (1)
- Barnes, Daniel R. (1)
- Barr, Cathy L. (1)
- Barwell, Julian (1)
- Bau, Claiton H.D. (1)
- Bauer, Michael (1)
- Bauer, Sebastian (1)
- Baumeister, Sarah (1)
- Baumgärtner, Daniel (1)
- Baune, Bernhard T. (1)
- Baur‐Streubel, Ramona (1)
- Beane Freeman, Laura E. (1)
- Beattie, Mary S. (1)
- Bedke, Tanja (1)
- Beeghly-Fadiel, Alicia (1)
- Beesley, Jonathan (1)
- Beilhack, Georg F. (1)
- Belangero, Sintia I. (1)
- Bellenguez, Céline (1)
- Bellgrove, Mark A. (1)
- Bellivier, Frank (1)
- Bellodi, Laura (1)
- Belotti, Muriel (1)
- Ben-Hur, Asa (1)
- Benarroch, Fortu (1)
- Bengesser, Susanne (1)
- Benoit, Joshua B. (1)
- Benso, Alfredo (1)
- Bergen, Arthur A. B. (1)
- Berger, Andreas (1)
- Berges, Carsten (1)
- Bergh, Florian Then (1)
- Bergsten, Emma (1)
- Berrio, Gabriel Bedoya (1)
- Berthele, Achim (1)
- Berthet, Pascaline (1)
- Bertone, Paul (1)
- Best, Lyle G. (1)
- Beudert, Burkhard (1)
- Bhat, Prajwal (1)
- Bialkowska, Katarzyna (1)
- Biederman, Joseph (1)
- Bielack, Stefan S. (1)
- Bielow, Chris (1)
- Bienvenu, Oscar J. (1)
- Biernacka, Joanna M. (1)
- Bisti, F. (1)
- Blanco, Ignacio (1)
- Blanco, Ingnacio (1)
- Blank, Bernd (1)
- Blank, Stephanie V. (1)
- Blein, Sophie (1)
- Blenau, Wolfgang (1)
- Bloch, Michael H. (1)
- Blok, Marinus J. (1)
- Blom, Rianne M. (1)
- Boettcher, Tobias (1)
- Bojesen, Anders (1)
- Bonadona, Valerie (1)
- Bonneau, Richard (1)
- Booth, Warren (1)
- Borg, Ake (1)
- Boroviak, Thorsten (1)
- Bouman, Katherine L. (1)
- Bowden, Donald W. (1)
- Brady, Angela (1)
- Bralten, Janita (1)
- Brandeis, Daniel (1)
- Breen, Gerome (1)
- Brem, Silvia (1)
- Brenner, Steven E. (1)
- Breslin, Paul A. S. (1)
- Bressan, Rodrigo A. (1)
- Brettschneider, Johannes (1)
- Brichant-Petitjean, Clara (1)
- Broderick, Avery E. (1)
- Broeks, Annegien (1)
- Bronte-Stewart, Helen M. (1)
- Brunet, Joan (1)
- Bruttel, Valentin S (1)
- Bruun, Ruth D. (1)
- Bryson, Kevin (1)
- Budman, Cathy L. (1)
- Bui, Elise (1)
- Buitelaar, Jan K. (1)
- Burkle, Laura A. (1)
- Burlock, Allison (1)
- Busatto, Geraldo F. (1)
- Butson, Christopher R. (1)
- Cabezas-Wallscheid, Nina (1)
- Cagnolo, Luciano (1)
- Caldés, Trinidad (1)
- Calender, Alain (1)
- Calkin, Cynthia V. (1)
- Camarena, Beatriz (1)
- Campa, Daniele (1)
- Campbell, Desmond (1)
- Campos, Brent R. (1)
- Cao, Renzhi (1)
- Capone, Gabriele L. (1)
- Cappi, Carolina (1)
- Carbonaro, Francis (1)
- Cardona Silgado, Julio C. (1)
- Cardoso, Vitor (1)
- Carnevalli, Larissa S. (1)
- Carter, Brian D. (1)
- Carter, Natalie J. (1)
- Casadio, Rita (1)
- Caspell, Richard (1)
- Castelao, Jose E. (1)
- Castellanos, Francisco X. (1)
- Castera, Laurent (1)
- Cath, Danielle C. (1)
- Cavallini, Maria C. (1)
- Cejuela, Juan M. (1)
- Cercignani, Mara (1)
- Chaim‐Avancini, Tiffany M. (1)
- Chan, Salina B. (1)
- Chan, Tsun L. (1)
- Chantiluke, Kaylita C. (1)
- Chao, Anne (1)
- Chao, Hsu (1)
- Chapman, Samuel (1)
- Chaves, Ryan (1)
- Chavira, Denise A. (1)
- Chen, Ching-Tai (1)
- Chen, Wang (1)
- Chen, Yii-Der Ida (1)
- Cheng, Andrew Tai Ann (1)
- Cheng, Jianlin (1)
- Chergui, Brahim (1)
- Childers, Christopher (1)
- Chillotti, Caterina (1)
- Chiquette, Jocelyne (1)
- Chizeck, Howard J. (1)
- Choi, Chang‐Yong (1)
- Choi, Ji-Yeob (1)
- Chouinard, Sylvian (1)
- Christakou, Anastasia (1)
- Cibrian-Uhalte, Elena (1)
- Cichon, Sven (1)
- Clark, Scott (1)
- Clark, Wyatt T. (1)
- Cleary, Daniel F. R. (1)
- Coelho, Luiis P. (1)
- Coelho, Luis Pedro (1)
- Coghill, David (1)
- Cohn, David E. (1)
- Cole, Shelley A. (1)
- Cole, Trevor (1)
- Comeau, Mary E. (1)
- Conti, David V. (1)
- Conzelmann, Annette (1)
- Cook, Edwin H. (1)
- Coric, Vladimir (1)
- Corines, Marina (1)
- Cortesi, Laura (1)
- Costea, Paul I (1)
- Costea, Paul I. (1)
- Coupier, Isabelle (1)
- Cox, Angela (1)
- Cox, David G. (1)
- Cox, Nancy J. (1)
- Cozzetto, Domenico (1)
- Cross, Simon S. (1)
- Crumière, Antonin Jean Johan (1)
- Cubillo, Ana I. (1)
- Cuenca, Miguelangel (1)
- Cullen, Bernadette A. (1)
- Cunningham, Julie (1)
- Cupertino, Renata B. (1)
- Curtis, Charles (1)
- Curtis, Jeffrey M. (1)
- Czerski, Piotr M. (1)
- Czudowska, Monika A. (1)
- D'Andrea, Daniel (1)
- Dandekar, Thomas (1)
- Danjean, Vincent (1)
- Dantas, Clarissa (1)
- Das, Sayoni (1)
- Davidson, Rosemarie (1)
- Davis, Lea K. (1)
- Davis, Thomas Seth (1)
- Dawson, Natalie L. (1)
- De Leeneer, Kim (1)
- De Luca, Antonella (1)
- DePaulo, J. Raymond (1)
- Dechnik‐Vázquez, Yanus A. (1)
- Deeb, Wissam (1)
- Deforce, Dieter (1)
- Deissler, Helmut (1)
- Del Valle, Jesus (1)
- Del Zompo, Maria (1)
- Delnatte, Capucine (1)
- Delorme, Richard (1)
- Denison, Timothy (1)
- Denny, Paul (1)
- Deny, Damiaan (1)
- Denys, Damiaan (1)
- Derks, Eske M. (1)
- Derst, Christian (1)
- Despriet, Dominiek D. G. (1)
- Dessimoz, Christophe (1)
- Detera-Wadleigh, Sevilla D. (1)
- Di Carlo, Stefano (1)
- DiSilvestro, Paul A. (1)
- Dicks, Ed (1)
- Dinh, Huyen (1)
- Diniz, Mateus Jose Abdalla (1)
- Dion, Yves (1)
- Dittrich, Marcus (1)
- Divers, Jasmin (1)
- Djakovic, Lara (1)
- Doboszewski, Juliusz (1)
- Doddapaneni, Harshavardhan (1)
- Dodson, Richard (1)
- Dogan, Tunca (1)
- Dolan, Amanda (1)
- Dolcetti, Riccardo (1)
- Dorkins, Huw (1)
- Dougherty, Darin D. (1)
- Downing, William M. (1)
- Doyle, Alysa E. (1)
- Drechsler, Christiane (1)
- Dreyfus, Helene (1)
- Dugan, Shannon (1)
- Duggirala, Ravi (1)
- Duncan, Elizabeth J. (1)
- Dunnig, Alison (1)
- Duran, Mercedes (1)
- Durda, Katarzyna (1)
- Durston, Sarah (1)
- Dölken, Lars (1)
- Döring, Kristina (1)
- Earl, Eric A. (1)
- Eason, Jacqueline (1)
- Eccles, Diana (1)
- Eckardt, Sigrid (1)
- Edenhofer, Frank (1)
- Edlund, Christopher K. (1)
- Eeles, Rosalind A. (1)
- Egberts, Karin (1)
- Einbeigi, Zakaria (1)
- Eisenman, Robert N. (1)
- Ekici, Arif B. (1)
- ElShal, Sarah (1)
- Elan, Camille (1)
- Elder, Jamee (1)
- Ellberg, Carolina (1)
- Elston, Robert C. (1)
- Engert, Stefanie (1)
- Epstein, Jeffery N. (1)
- Erhard, Florian (1)
- Essers, Marieke A. G. (1)
- Etain, Bruno (1)
- Ethofer, Thomas (1)
- Ettrich, Barbara (1)
- Evans, Jay D. (1)
- Evans, Patrick (1)
- Eyert, V. (1)
- Fair, Damien A. (1)
- Faiss, Jürgen H. (1)
- Falda, Marco (1)
- Fallarino, Francesca (1)
- Fallgatter, Andreas J. (1)
- Fang, Hai (1)
- Faraone, Stephen V. (1)
- Fender, Rob P. (1)
- Feng, Shou (1)
- Fernandez, Thomas V. (1)
- Fernández, José M. (1)
- Ferrari, Carlo (1)
- Ferreira, Manuel A. (1)
- Figueroa, Jonine (1)
- Fineberg, Elena (1)
- Finn, Robert D. (1)
- Fisher, Simon E. (1)
- Fitzpatrick, Garret (1)
- Fletcher, Olivia (1)
- Fontana, Paolo (1)
- Foo, Claire (1)
- Foote, Kelly D. (1)
- Foster, Paul J. (1)
- Fostira, Florentia (1)
- Foulger, Rebecca E. (1)
- Foulkes, William (1)
- Fountzilas, George (1)
- Fox, Stephen (1)
- Francks, Clyde (1)
- Franke, Barbara (1)
- Fredericksen, Zachary (1)
- Freedman, Barry I. (1)
- Freimer, Nelson B. (1)
- Friebel, Tara M. (1)
- Friedberg, Iddo (1)
- Friedel, Caroline C. (1)
- Friedlander, Michael (1)
- Friedrich, Markus (1)
- Frisén, Louise (1)
- Fritschi, Lin (1)
- Frodl, Thomas (1)
- Fromm, Christian M. (1)
- Frye, Mark A. (1)
- Fuchs, Jörg (1)
- Fuentes‐Ramirez, Andrés (1)
- Fullerton, Jan (1)
- Funk, Christopher S. (1)
- Gabaldon, Toni (1)
- Gabel, Matt C. (1)
- Gadelha, Ary (1)
- Gadzicki, Dorothea (1)
- Galison, Peter (1)
- Gallagher, Patience J. (1)
- Gandhi, Kamal J. K. (1)
- Gao, Chi (1)
- Garcia, Encarna B. Gómez (1)
- Gard, Sébastien (1)
- Garnham, Julie (1)
- Garrido, Helena (1)
- Gauthier-Villars, Marion (1)
- Gehring, Catherine (1)
- Geis, Christian (1)
- Geller, Daniel (1)
- Gemovic, Branislava (1)
- Georgiev, Kostadin B. (1)
- Gerhardt, Greg A. (1)
- Geschwantler Kaulich, Daphne (1)
- Giannini, Giuseppe (1)
- Gibbs, Richard A. (1)
- Gille, Johannes J. P. (1)
- Gillis, Jesse (1)
- Gimbutas, Mark (1)
- Ginter, Filip (1)
- Giollo, Manuel (1)
- Giordano, James J. (1)
- Giovannini, Gloria (1)
- Girard, Simon L. (1)
- Glahn, David C. (1)
- Glisic, Sanja (1)
- Godwin, Andrew K (1)
- Goes, Fernando S. (1)
- Gogberashvili, Tinatin (1)
- Goldberg, Tatyana (1)
- Golmard, Lisa (1)
- Gondhalekar, Ameya D. (1)
- Gong, Qingtian (1)
- Gongalsky, Konstantin B. (1)
- González-Neira, Anna (1)
- Gorbunova, Anastasiya Y. (1)
- Gough, Julian (1)
- Grabe, Hans J. (1)
- Grados, Marco A. (1)
- Graf, Carolin (1)
- Gramer, Eugen (1)
- Greenberg, Benjamin D. (1)
- Greenberg, Cathryn H. (1)
- Greene, Casey S. (1)
- Gregory, Helen (1)
- Grevet, Eugenio H. (1)
- Grigoroiu-Serbanescu, Maria (1)
- Grill, Warren M. (1)
- Grof, Paul (1)
- Gross-Tsur, Varda (1)
- Gruber, Oliver (1)
- Grässer, Friedrich (1)
- Gschwantler-Kaulich, Daphne (1)
- Gujar, Hemant (1)
- Gunduz, Aysegul (1)
- Guo, Xiuqing (1)
- Gupta, A. (1)
- Guthke, Kersten (1)
- Gómez, José L. (1)
- Göbel, Margarete (1)
- Güntherodt, G. (1)
- Haas, Simon (1)
- Haavik, Jan (1)
- Haddad, Stephen (1)
- Haeberle, Lothar (1)
- Hagan, Richard W. (1)
- Haggard, Daryl (1)
- Hahnen, Eric (1)
- Hakala, Kai (1)
- Hall, Lynsey S. (1)
- Hallberg, Emily (1)
- Hallmen, Erika (1)
- Hammond, Christopher J. (1)
- Hamp, Tobias (1)
- Han, Yi (1)
- Hanna, Gregory L. (1)
- Hanson, Jodi (1)
- Hanson, Robert L. (1)
- Hardouin, Agnès (1)
- Harrison, Neil A. (1)
- Hart, Steven (1)
- Hartman, Catharina A. (1)
- Hartman, Mikael (1)
- Hartung, Hans P. (1)
- Hartwig, Maite (1)
- Hashimoto, Ryota (1)
- Hauke, Jan (1)
- Hauser, Joanna (1)
- Haworth, Kari (1)
- Hayrettin, Christoph A. (1)
- Hayward, Matthew R. (1)
- He, Wei (1)
- Healay, Sue (1)
- Heilbronner, Urs (1)
- Heiman, Gary A. (1)
- Hein, Alexander (1)
- Heintz-Buschart, Anna (1)
- Hellwig, Kerstin (1)
- Hemmer, Bernhard (1)
- Hemmings, Sian M. J. (1)
- Hendershot, Jacob M. (1)
- Hennig, Thomas (1)
- Herbert, Cornelia (1)
- Herzog, Josef (1)
- Heslenfeld, Dirk J. (1)
- Heutink, Peter (1)
- Hewitt, Alex W. (1)
- Heyworth, Jane (1)
- Hieta, Reija (1)
- Hillemanns, Peter (1)
- Hingamp, Pascal (1)
- Hoban, Rebecca (1)
- Hoekstra, Pieter J. (1)
- Hoffmann, Frank (1)
- Hoffmann, Michael Marcus (1)
- Hofman, Albert (1)
- Hofstadt-van Oy, Ulrich (1)
- Hohmann, Sarah (1)
- Hollestelle, Antoinette (1)
- Holm, Liisa (1)
- Hoogman, Martine (1)
- Hooning, Maartje J. (1)
- Hoover, Robert N. (1)
- Hosseini, S. Mohsen (1)
- Hottel, Benjamin A. (1)
- Hou, Liping (1)
- Houdayer, Claude (1)
- Houghton, Catherine (1)
- Hounie, Ana G. (1)
- Houston, Janice (1)
- Howard, Barbara V. (1)
- Howell, Tony (1)
- Hsu, Wen-Lian (1)
- Huang, Huateng (1)
- Huber, Wolfgang (1)
- Huerta-Cepas, Jaime (1)
- Hughes, Daniel S.T. (1)
- Humphreys, Keith (1)
- Huntley, Rachael P. (1)
- Huzarski, Tomasz (1)
- Hylander, Kristoffer (1)
- Hys, Pirro G. (1)
- Håkansson, Niclas (1)
- Hölzl, R. (1)
- Høvik, Marie F. (1)
- Iannitti, Rossana G. (1)
- Igo, Jr, Robert P. (1)
- Ikram, M. Kamran (1)
- Illmann, Cornelia (1)
- Ioannidis, Panagiotis (1)
- Ipp, Eli (1)
- Issaoun, Sara (1)
- Ito, Hidemi (1)
- Ivady, Gabriella (1)
- Iwasaki, Motoki (1)
- Iyengar, Sudha K. (1)
- Izatt, Luise (1)
- Izquierdo, Angel (1)
- Jager, Agnes (1)
- Jahanshad, Neda (1)
- Jahnukainen, Kirsi (1)
- Jakimovska, Milena (1)
- Jamain, Stéphane (1)
- James, Paul (1)
- Jankovic, Joseph (1)
- Jankowitz, Rachel C. (1)
- Janni, Wolfgang (1)
- Jansonius, Nomdo M. (1)
- Janssen, Sarah F. (1)
- Jarius, Sven (1)
- Jaworska, Katarzyna (1)
- Jenike, Micheal A. (1)
- Jennings, Emily C. (1)
- Jentzsch, IMV (1)
- Jentzsch, Iris M. Vargas (1)
- Jernigan, Terry L. (1)
- Jiang, Yuxiang (1)
- Jimenez-Shahed, Joohi (1)
- Johannsson, Oskar Th (1)
- Johnson, Nichola (1)
- Johnston, J. Spencer (1)
- Johnston, Paul R. (1)
- Jones, David T. (1)
- Jones, Jeffery W. (1)
- Jones, Michael E. (1)
- Joseph, Vijai (1)
- Judy, Jack W. (1)
- Jules, Erik S. (1)
- Jung, Audrey (1)
- Jønson, Lars (1)
- Jürges, Christopher S. (1)
- Kaaks, Rudolf (1)
- Kaewphan, Suwisa (1)
- Kahanda, Indika (1)
- Kahn, Jean-Pierre (1)
- Kang, Daehee (1)
- Kansakar, Lakesh (1)
- Kao, W. H. Linda (1)
- Kapoor, Pooja Middha (1)
- Karacsony, Kinga (1)
- Kardatzki, Bernd (1)
- Karkashadze, Georgii (1)
- Karlan, Bethy Y. (1)
- Karlbauer, G. (1)
- Karolak, M. (1)
- Kassem, Layla (1)
- Kato, Tadafumi (1)
- Kauff, Noah (1)
- Kaufman, Bella (1)
- Kazanowska, Bernarda (1)
- Keenan, Clare L. (1)
- Kegel, Thomas (1)
- Keller, Benjamin J. (1)
- Kelly, Clare (1)
- Kelsoe, John R. (1)
- Kempa, Stefan (1)
- Kennedy, James L. (1)
- Kennedy, M. John (1)
- Kern, Peter (1)
- Kets, Carolien M. (1)
- Khan, Ishita K. (1)
- Khila, Abderrahman (1)
- Kihara, Daisuke (1)
- Kiiski, Johanna I. (1)
- Kimmel, Paul L. (1)
- King, Robert A. (1)
- Kitahara, Cari M. (1)
- Kittel-Schneider, Sarah (1)
- Klag, Michael J. (1)
- Klassen, Bryan T. (1)
- Klaver, Caroline C. W. (1)
- Kleinschnitz, Christoph (1)
- Kleiter, Ingo (1)
- Klingebiel, Thomas (1)
- Kliwicki, Sebastian (1)
- Kloz, Ulrich (1)
- Knowler, William C. (1)
- Knowles, James A. (1)
- Ko, Yon-Dschun (1)
- Kohls, Gregor (1)
- Kohn, Orly F. (1)
- Konkashbaev, Anuar I. (1)
- Konrad, Kerstin (1)
- Kontny, Udo (1)
- Koo, Da Chen Emily (1)
- Korobushkin, Daniil I. (1)
- Koscielniak, Ewa (1)
- Kosel, Matthew (1)
- Koskinen, Patrik (1)
- Koutros, Stella (1)
- Kovalev, Yuri Y. (1)
- Kramer, Gero (1)
- Kramer, Rogier (1)
- Kramm, Christof M. (1)
- Kremeyer, Barbara (1)
- Kretzler, Matthias (1)
- Kuempfel, Tania (1)
- Kuerten, Stefanie (1)
- Kuntsi, Jonna (1)
- Kuo, Po-Hsiu (1)
- Kurlan, Roger (1)
- Kurth, Valerie (1)
- Kurzwart, Miriam (1)
- Kusumi, Ichiro (1)
- Köster, Kajar (1)
- Künzig, Florian W. H. (1)
- L'hernault, Anne (1)
- Ladenstein, Ruth (1)
- Laje, Gonzalo (1)
- Landthaler, Markus (1)
- Langefeld, Carl D. (1)
- Langel, Stefan (1)
- Langevin, Jean-Philippe (1)
- Lanham, Joseph Drew (1)
- Lanzagorta, Nuria (1)
- Lasa, Adriana (1)
- Latgé, Jean-Paul (1)
- Lauda, Florian (1)
- Lautenbacher, S. (1)
- Lavebratt, Catharina (1)
- Lavezzo, Enrico (1)
- Lazarina, Maria (1)
- Lazaro, Luisa (1)
- Le Marchand, Loic (1)
- Leak, Tennille S. (1)
- Leckband, Susan G. (1)
- Leckman, James F. (1)
- Lee, Adam (1)
- Lee, Chien-Yueh (1)
- Lee, David (1)
- Lee, S. Hong (1)
- Lee, Sandra L. (1)
- Leehey, David J. (1)
- Lees, Jonathan G. (1)
- Lefol, Cedrick (1)
- Legge, Duncan (1)
- Lehner, Paul J. (1)
- Lejbkowicz, Flavio (1)
- Lemij, Hans G. (1)
- Lennertz, Leonhard (1)
- Lepore, Rosalba (1)
- Lera‐Miguel, Sara (1)
- Leroux, Dominique (1)
- Leroux,, Dominique (1)
- Lesch, Klaus‐Peter (1)
- Leslie, Goska (1)
- Lesueur, Fabienne (1)
- Leverkus, Alexandro B. (1)
- Levis, Aviad (1)
- Li, Biao (1)
- Li, Jingmei (1)
- Li, Man (1)
- Li, Simone S. (1)
- Liang, Chunguang (1)
- Lico, Rocco (1)
- Liebetrau, Martin (1)
- Ligtenberg, Marjolinjin J. L. (1)
- Lin, Alexandra (1)
- Lin, Han (1)
- Lindblom, Annika (1)
- Lindenmayer, David (1)
- Lindor, Noralane M. (1)
- Lindor, Noralene M. (1)
- Linet, Martha (1)
- Linial, Michal (1)
- Linker, Ralf A. (1)
- Lister, Matthew L. (1)
- Liu, Chunyu (1)
- Ljungman, Gustaf (1)
- Lo, Wing-Yee (1)
- Lobanov, Andrei P. (1)
- Lochner, Christine (1)
- Lophatananon, Artitaya (1)
- Louza, Mario R. (1)
- Lovering, Ruth C. (1)
- Lowe, Thomas L. (1)
- Lu, Karen H. (1)
- Lubinski, Jan (1)
- Lubinski,, Jan (1)
- Lundervold, Astri J. (1)
- Léoné, Mélanie (1)
- López Jaramillo, Carlos A. (1)
- Macciardi, Fabio (1)
- Macgregor, Stuart (1)
- Machackova, Eva (1)
- Mackey, David A. (1)
- Magrane, Michele (1)
- Maietta, Paolo (1)
- Maistrenko, Oleksandr M. (1)
- Maiwald, Frank (1)
- Maj, Mario (1)
- Makalic, Enes (1)
- Malafosse, Alain (1)
- Malhotra, Alka (1)
- Malpas, Charles B (1)
- Manchia, Mirko (1)
- Marcet-Houben, Marina (1)
- Marcoci, Alexandru (1)
- Mardin, Christian Y. (1)
- Markoff, Sera (1)
- Markov, Nadja Bogdanova (1)
- Marra, Daniel Magnabosco (1)
- Martelli, Pier Luigi (1)
- Martens, Niels C. M. (1)
- Martin, Maria J. (1)
- Martinez, Elena (1)
- Martinsson, Lina (1)
- Martín‐Pinto, Pablo (1)
- Marziniak, Martin (1)
- Mastrobuoni, Guido (1)
- Masui, Takuya (1)
- Matheson, Nicholas J. (1)
- Mathews, Carol A. (1)
- Matricardi, Laura (1)
- Matsuo, Keitaro (1)
- Mattos, Paulo (1)
- Maurer, Tabea (1)
- Mavroudis, Dimitrios (1)
- Mavroudis, Dimitris (1)
- Mayberg, Helen S. (1)
- McCann, Emma (1)
- McCarthy, Hazel (1)
- McCracken, James T. (1)
- McGrath, Lauren M. (1)
- McGuffin, Peter (1)
- McLaughlin, K John (1)
- McMahon, Francis J. (1)
- McMahon, William (1)
- Meave, Jorge A. (1)
- Medland, Sarah E. (1)
- Mehryary, Farrokh (1)
- Melidoni, Anna N. (1)
- Melin, Beatrice (1)
- Melloni, Guilia (1)
- Melms, Arthur (1)
- Mende, Daniel R (1)
- Menegatti, Jennifer (1)
- Menegazzi, Pamela (1)
- Mesiti, Marco (1)
- Metz, Imke (1)
- Michailidou, Kyriaki (1)
- Miguel, Euripedes C. (1)
- Milanese, Alessio (1)
- Miller, Austin (1)
- Minneci, Federico (1)
- Miron, Alexander (1)
- Mitchell, Alex L (1)
- Mitchell, Paul (1)
- Mitchell, Philip B. (1)
- Mittapalli, Omprakash (1)
- Mizuno, Yosuke (1)
- Moeller, Sanne Traasdahl (1)
- Moessner, Rainald (1)
- Mogilner, Alon Y. (1)
- Mohan, M. (1)
- Mohd Taib, Nur Aishah (1)
- Mokhtari, Zeinab (1)
- Moldova, Ioana (1)
- Mondimore, Frank (1)
- Monteleone, Palmiero (1)
- Montgomery, Grant W. (1)
- Mooney, Sean D. (1)
- Moreau, Yves (1)
- Moreno, Fernando (1)
- Moretti, Marco (1)
- Morgan, Jubel (1)
- Moserle, Lidia (1)
- Mottok, Anja (1)
- Muir, Kenneth (1)
- Muller, Heike (1)
- Murali, Shwetha C. (1)
- Muranen, Taru A. (1)
- Murphy, Dennis L. (1)
- Murray, Alex (1)
- Mutowo-Meullenet, Prudence (1)
- Muzny, Donna M. (1)
- März, Winfried (1)
- Müller, Albrecht M (1)
- Münch, Christoph (1)
- Münter, Marc (1)
- Naarden, Allan L. (1)
- Nagar, Neil M. (1)
- Nair, Viji (1)
- Nallet, Audrey (1)
- Nam, Hyun‐Young (1)
- Namazova‐Baranova, Leyla (1)
- Narayan, Ramesh (1)
- Narod, Steven A. (1)
- Natarajan, Priyamvada (1)
- Nauen, Ralf (1)
- Navratilova, Marie (1)
- Neale, Benjamin M. (1)
- Negrin, Robert S. (1)
- Nelson, David R. (1)
- Nelson, Robert G. (1)
- Nepusz, Tamás (1)
- Nestadt, Gerald (1)
- Neuhaus, Oliver (1)
- Neuner, Maria (1)
- Nevelsteen, Ines (1)
- Neven, Patrick (1)
- Newhouse, Stephen J. (1)
- Newman, William G. (1)
- Nicholas, Susanne B. (1)
- Nichols, Tiffany (1)
- Nicolau, Rosa (1)
- Nicolini, Humberto (1)
- Niehaus, Sabine (1)
- Nigg, Joel T. (1)
- Niggli, Felix (1)
- Nikitina-Zake, Liene (1)
- Ning, Wei (1)
- Nogues, Catherine (1)
- Noto, Cristiano (1)
- Novotny, Stephanie E. (1)
- Novák, Tomás (1)
- O'Gorman Tuura, Ruth L. (1)
- O'Reilly, Paul F. (1)
- Oates, Matt (1)
- Oberwelland Weiss, Eileen (1)
- Obrist, Martin K. (1)
- Ochoa, William Cornejo (1)
- Ofer, Dan (1)
- Offit, Kenenth (1)
- Oh, Michael (1)
- Okun, Michael S. (1)
- Olshan, Andrew F. (1)
- Olson, Janet E. (1)
- Oosterlaan, Jaap (1)
- Oosterwijk, Jan C. (1)
- Ophoff, Roel A. (1)
- Oppenheimer, Aaron (1)
- Oranje, Bob (1)
- Orengo, Christine A. (1)
- Oron, Tal Ronnen (1)
- Osiecki, Lisa (1)
- Ostrem, Jill L. (1)
- Ota, Vanessa K. (1)
- Ott, Mark-Christoph (1)
- Ozaki, Norio (1)
- Ozcelik, Hilmi (1)
- O’Brien, Stephen J. (1)
- Paccanaro, Alberto (1)
- Pahl, Madeleine V. (1)
- Pakstis, Andrew J. (1)
- Palli, Domenico (1)
- Palli, Subba R. (1)
- Paloyelis, Yannis (1)
- Paluch, Shani Shimon (1)
- Palumbo, Daniel C. M. (1)
- Panfilio, Kristen A. (1)
- Paoli, Lucas (1)
- Parekh, Rulan S. (1)
- Park, Sue K. (1)
- Parsons, Michael T. (1)
- Pasini, Barbara (1)
- Pastinen, Tomi (1)
- Pasutto, Francesca (1)
- Patel, Hamel (1)
- Paterson, Andrew D. (1)
- Pato, Carlos N. (1)
- Pato, Michele T. (1)
- Paul, Friedemann (1)
- Paul, S. (1)
- Pauls, David L. (1)
- Pavlidis, Paul (1)
- Peissel, Bernhard (1)
- Peixoto, Ana (1)
- Pellkofer, Hannah (1)
- Penfold-Brown, Duncan (1)
- Peock, Susan (1)
- Perkins, Jo (1)
- Perlis, Roy H. (1)
- Perovic, Vladmir (1)
- Pesce, Dominic W. (1)
- Peschel, Nicolai (1)
- Petanidou, Theodora (1)
- Peterlongo, Peter (1)
- Peto, Julian (1)
- Pezzolesi, Marcus G. (1)
- Pfennig, Andrea (1)
- Piacentini, John (1)
- Pichler, Klemens (1)
- Picon, Felipe A. (1)
- Pinto, Pedro (1)
- Piovesan, Damiano (1)
- Pittenger, Christopher (1)
- Platte, Petra (1)
- Platte, Radke (1)
- Plessen, Kerstin J. (1)
- Poelchau, Monica (1)
- Pohl-Rescigno, Esther (1)
- Politano, Gianfranco (1)
- Pollak, Yehunda (1)
- Ponce, Francisco A. (1)
- Pons, Pere (1)
- Porteous, Mary E. (1)
- Postema, Merel C. (1)
- Posthuma, Danielle (1)
- Potash, James B. (1)
- Potts, Simon G. (1)
- Pourfar, Michael (1)
- Predel, Reinhard (1)
- Prendergast, Áine M. (1)
- Prieur, Fabienne (1)
- Profeta, G. (1)
- Profiti, Giuseppe (1)
- Prusty, Bhupesh (1)
- Pujana, Miguel Angel (1)
- Pujana, Miquel Angel (1)
- Pujol, Pascal (1)
- Qu, Jiaxin (1)
- Qureischi, Musga (1)
- Rack, Brigitte (1)
- Radivojac, Predrag (1)
- Raje, Kapil R. (1)
- Ramdas, Wishal D. (1)
- Ramos‐Quiroga, J. Antoni (1)
- Rapoport, Irina B. (1)
- Rappaport-Fuerhauser, Christine (1)
- Rappoport, Nadav (1)
- Rashid, Muhammad U. (1)
- Rasooly, Rebekah S. (1)
- Rauch, Scott L. (1)
- Re, Matteo (1)
- Recks, Mascha S. (1)
- Refki, Peter Nagui (1)
- Rehman, Hafeez Ur (1)
- Reich-Erkelenz, Daniela (1)
- Reinhardt, Klaus (1)
- Reininghaus, Eva (1)
- Reis, Andre (1)
- Reneman, Liesbeth (1)
- Renner, Tobias J. (1)
- Rennert, Hedy S. (1)
- Resnik, Valentina (1)
- Restrepo, Sandra C. Mesa (1)
- Reu, Simone (1)
- Reus, Victor I. (1)
- Reuss, Reinhard (1)
- Reyes, Alejandro (1)
- Rhoades, Paul R. (1)
- Ribeiro, Jose M.C. (1)
- Richards, Stephen (1)
- Richardson, Sara (1)
- Richter, Clark (1)
- Richter, Lothar (1)
- Richter, Margaret A. (1)
- Riddle, Mark A. (1)
- Rietschel, Marcella (1)
- Ringelstein, Marius (1)
- Rioja, María J. (1)
- Risch, Harvey A. (1)
- Ritz, Miriam (1)
- Rivadeneira, Fernando (1)
- Rizzolo, Piera (1)
- Robertson, Hugh M. (1)
- Robertson, Mary M. (1)
- Robinson, Peter N. (1)
- Rodriguez, Gustavo C. (1)
- Rogalev, V. A. (1)
- Romani, Luigina (1)
- Romero, Alfonso E. (1)
- Romero, Roxana (1)
- Rommer, Paulus S. (1)
- Rosa, Pedro G.P. (1)
- Rosenberg, David (1)
- Rosenberg, Paul B. (1)
- Rosendale, Andrew J. (1)
- Rossi, Marvin A. (1)
- Rossi, Peter J. (1)
- Rost, Burkhard (1)
- Rosàrio, Maria C. (1)
- Rotimi, Charles N. (1)
- Rotter, Jerome I. (1)
- Rowell, David (1)
- Rubia, Katya (1)
- Ruddy, Kathryn J. (1)
- Ruebner, Matthias (1)
- Ruhrmann, Stephan (1)
- Ruiz-Linares, Andreas (1)
- Ruprecht, Klemens (1)
- Ruscheweyh, Hans-Joachim (1)
- Russo, Antonio (1)
- Rutkowski, Andrzej J. (1)
- Rybakowski, Janusz K. (1)
- Sahraeian, Sayed M. E. (1)
- Saifutdinov, Ruslan A. (1)
- Salakoski, Tapio (1)
- Salamov, Asaf (1)
- Salazar, Guillem (1)
- Saloma, Andiara (1)
- Sampaio, Aline S. (1)
- Samuels, Jack (1)
- Sand, Sharon R. (1)
- Sanden, Kristin (1)
- Sanders, Nathan J. (1)
- Sandor, Paul (1)
- Sangiovanni, G. (1)
- Santoro, Marcos L. (1)
- Santos, Maria Emilia (1)
- Santos, Xavier (1)
- Sarrel, Kara (1)
- Sasidharan, Rajkumar (1)
- Savarese, Antonella (1)
- Savino, Alessandro (1)
- Sawyer, Elinor J. (1)
- Schal, Coby (1)
- Schalling, Martin (1)
- Scharf, Jeremiah M. (1)
- Scharf, Michael E. (1)
- Scheer, Monika (1)
- Schelling, Jeffrey R. (1)
- Schindler, Detlev (1)
- Schippling, Sven (1)
- Schlegel, Paul G (1)
- Schlegel, Paul G. (1)
- Schmiedgen, Katharina (1)
- Schmitt, Jessica (1)
- Schmitt, T. (1)
- Schmutzler, Rita Katharina (1)
- Schneider, Michael O. (1)
- Schoemaker, Minouk J. (1)
- Schofield, Peter R. (1)
- Schorn, Corinna (1)
- Schrantee, Anouk (1)
- Schubert, Oliver K. (1)
- Schulz, Stephan (1)
- Schulze, Thomas G. (1)
- Schweizer, Barbara (1)
- Schweren, Lizanne J.S. (1)
- Scognamiglio, Roberta (1)
- Scott, Christopher (1)
- Scuvera, Giulietta (1)
- Sedeño-Cortés, Adriana E. (1)
- Sedor, John R. (1)
- Seemüller, Florian (1)
- Segota, Ena (1)
- Segura, Pedro Perez (1)
- Seitz, Jochen (1)
- Seldin, Michael F. (1)
- Severino, Giovanni (1)
- Seymour, Lisa R. (1)
- Seynaeve, Caroline (1)
- Sghaier, Essia (1)
- Shah, Vallabh O. (1)
- Sharan, Malvika (1)
- Shasha, Dennis (1)
- Shaw, Philip (1)
- Shen, Chen-Yang (1)
- Sheppard, Broke (1)
- Shugart, Yin Yao (1)
- Shukla, Jayendra Nath (1)
- Shute, Jonathan B. (1)
- Shypitsyna, Aleksandra (1)
- Sieb, Jörn P. (1)
- Silburn, Peter A. (1)
- Silk, Tim J. (1)
- Sillitoe, Ian (1)
- Silvestri, Valentina (1)
- Singer, Harvey S. (1)
- Sirén, Anna-Leena (1)
- Skokauskas, Norbert (1)
- Skunca, Nives (1)
- Skytte, Anne-Bine (1)
- Slager, Susan (1)
- Slager, Susan L. (1)
- Slaney, Claire (1)
- Small, Laurie (1)
- Smichkoska, Snezhana (1)
- Smiles, Adam M. (1)
- Smit, Jan H. (1)
- Smith, Austin (1)
- Smith, Gwenn S. (1)
- Smith, Michael W. (1)
- Smithers, Ben (1)
- Smoller, Jordan W. (1)
- Sobhani, Iradj (1)
- Sobol, Hagay (1)
- Sokolenko, Anna P. (1)
- Soliva Vila, Juan C. (1)
- Sornin, Valerie (1)
- Southey, Melissa (1)
- Sparber-Sauer, Monika (1)
- Spriewald, Bernd (1)
- Spugnesi, Laura (1)
- Squassina, Alessio (1)
- Stamm, Thomas (1)
- Stangel, Martin (1)
- Starr, Philip A. (1)
- Steel, Zachary (1)
- Steele, Jo (1)
- Stein, Dan J. (1)
- Stenmark-Askmalm, Marie (1)
- Stern, Amos (1)
- Sternberg, Michael J. E. (1)
- Stevens, Kristen (1)
- Stevens, Michael C. (1)
- Stewart, S. Evelyn (1)
- Stopkova, Pavla (1)
- Stravropoulou, Alexandra V. (1)
- Strengman, E. (1)
- Strian, F. (1)
- Strocov, V. N. (1)
- Struchalin, Maksim (1)
- Sudre, Gustavo (1)
- Sukiennicki, Grzegorz (1)
- Supek, Fran (1)
- Surowy, Harald (1)
- Szuter, Elise M. (1)
- Tabares, Paula (1)
- Tamimi, Rulla M. (1)
- Tamm, Leanne (1)
- Targoni, Oleg S. (1)
- Tavella, Julia (1)
- Taylor, Jack A. (1)
- Taylor, Kent D. (1)
- Tchatchou, Andrine (1)
- Teo, Soo H. (1)
- Teo, Soo-Hwang (1)
- Tessier, Daniel (1)
- Teule, Alex (1)
- Thameem, Farook (1)
- Thelander, Margo (1)
- Thier, Marc Christian (1)
- Thomas, Gilles (1)
- Thompson, Paul M. (1)
- Thorn, Simon (1)
- Thornley-Brown, Denyse P. (1)
- Thresher, Ann C. (1)
- Thöne, Kathrin (1)
- Tian, Weidong (1)
- Tibiletti, Maria Grazia (1)
- Tighe, Sarah K. (1)
- Tischfield, Jay A. (1)
- Tognazzo, Silvia (1)
- Tollenaar, Rob A. E. M. (1)
- Tommasi, Stefania (1)
- Topouzis, Fotis (1)
- Topp, Max S. (1)
- Toppo, Stefano (1)
- Torres-Mejía, Gabriela (1)
- Tortorella, Alfonso (1)
- Tosatto, Silvio C. E. (1)
- Tovar‐Moll, Fernanda (1)
- Tramontano, Anna (1)
- Tranchevent, Léon-Charles (1)
- Trebst, Corinna (1)
- Tress, Michael L. (1)
- Troester, Melissa A. (1)
- Truitt, Barbara J. (1)
- Trumpp, Andreas (1)
- Tsugane, Shoichiro (1)
- Tumani, Hayrettin (1)
- Turecki, Gustavo (1)
- Törönen, Petri (1)
- Uhrhammer, Nancy (1)
- Uitterlinden, Andre G. (1)
- Untch, Michael (1)
- Valencia Duarte, Ana V. (1)
- Valencia, Alfonso (1)
- Valentini, Giorgio (1)
- Vallada, Homero (1)
- Van Horne, Craig (1)
- Van Le, Linda (1)
- Van Maerken, Tom (1)
- Van Nieuwerburgh, Flip (1)
- Vance, Alasdair (1)
- Vargo, Edward L. (1)
- Varon-Mateeva, Raymenda (1)
- Vasickova, Petra (1)
- Vaszko, Tibor (1)
- Veauthier, Christian (1)
- Veenstra-VanderWeele, Jeremy (1)
- Vega, Ana (1)
- Veljkovic, Nevena (1)
- Veljkovic, Veljko (1)
- Venat-Bouvet, Laurence (1)
- Vencio, Ricardo Z. N. (1)
- Verhoef, Senno (1)
- Verspoor, Karin M. (1)
- Viala, Sèverine (1)
- Viel, Alexandra (1)
- Vilarroya, Oscar (1)
- Viljur, Mari‐Liis (1)
- Vincent, Daniel (1)
- Vingerling, Johannes R. (1)
- Viswanathan, Ananth C. (1)
- Vives‐Gilabert, Yolanda (1)
- Vogel, Jörg (1)
- Voigt, Anita Y. (1)
- Vokuhl, Christian (1)
- Volkmann, Jens (1)
- Volorio, Sara (1)
- Vucetic, Slobodan (1)
- Wagle Shukla, Aparna (1)
- Wagner, Michael (1)
- Walker, Harrison C. (1)
- Walker, Lisa (1)
- Walsh, Christine (1)
- Wand, Dorothea (1)
- Wandinger, Klaus P. (1)
- Wang, Jie Jin (1)
- Wang, Xianshu (1)
- Wang, Ying (1)
- Wang, Zheng (1)
- Wang-Gohrke, Shan (1)
- Wanner, Christoph (1)
- Wass, Mark N. (1)
- Waterhouse, Robert M. (1)
- Weaver, Joellen (1)
- Weber, Bernhard H. F. (1)
- Wegener, Christian (1)
- Weil, E. Jennifer (1)
- Weintroub, Jonathan (1)
- Weirauch, Matthew T. (1)
- Weisschuh, Nicole (1)
- Welge-Lüssen, Ulrich (1)
- Wendenburg, Clara (1)
- Wendland, Jens R. (1)
- Wermelinger, Beat (1)
- Wernig, Sebastian (1)
- Werren, John H. (1)
- Wessalowski, Rüdiger (1)
- Westenberg, Herman G. M. (1)
- Wheeler, David (1)
- Whisnant, Adam W. (1)
- Wielgus, Maciek (1)
- Wijnen, Juul T. (1)
- Wildemann, Brigitte (1)
- Wilke, Christian (1)
- Willemse-Assink, Jacqueline J. M. (1)
- Wilmes, Paul (1)
- Winkelmann, Alexander (1)
- Winkler, Cheryl A. (1)
- Winqvist, Robert (1)
- Wirbel, Jakob (1)
- Wischhusen, Jörg (1)
- Wolfs, Roger C. W. (1)
- Wolk, Alicja (1)
- Wong, Tien Y. (1)
- Worley, Kim C. (1)
- Wright, Adam (1)
- Wunsch, Marie (1)
- Wyler, Emanuel (1)
- Wölfl, Matthias (1)
- Wörsdörfer, Philipp (1)
- Yang, Haixuan (1)
- Yang, Jian (1)
- Yang, Xiaohong R. (1)
- Yoncheva, Yuliya N. (1)
- Yoon, Sook-Yee (1)
- Young, Terri L. (1)
- Youngs, Noah (1)
- Younsi, Ziri (1)
- Yu, Dongmei (1)
- Yu, Jyh-Cherng (1)
- Zaffaroni, Daniela (1)
- Zager, Philip G. (1)
- Zaitsev, Andrey S. (1)
- Zakeri, Pooya (1)
- Zandi, Peter P. (1)
- Zanetti, Marcus V. (1)
- Zanna, Ines (1)
- Zdobnov, Evgeny M. (1)
- Zeiser, Robert (1)
- Zenkel, Matthias (1)
- Zentner, Christian (1)
- Zettl, Uwe K (1)
- Zhang, Shanshan (1)
- Zhao, Chaoyang (1)
- Zhong, Zhaolong (1)
- Zhou, Jing-Jiang (1)
- Zhou, Yuanpeng (1)
- Zhu, Fang (1)
- Zidan, Jamal (1)
- Ziegler, Georg C. (1)
- Ziemann, Ulf (1)
- Zilles, David (1)
- Zimmer, Ralf (1)
- Ziv, Elad (1)
- Zlowocka-Perlowska, Elzbieta (1)
- Zorn, Kristin K. (1)
- de Beaufort, Carine (1)
- de Hemptine, Coralie (1)
- de Jong, Paulus T. V. M. (1)
- de Jong, Simone (1)
- de Pauw, Antoine (1)
- de Zeeuw, Patrick (1)
- del Pozo, Angela (1)
- dos-Santos-Silva, Isabel (1)
- ten Brink, Jacoline B. (1)
- van Asperen, Christi J. (1)
- van Deurzen, Carolien H. M. (1)
- van Dijk, Aalt D. J. (1)
- van Duijn, Cornelia M. (1)
- van Erp, Theo G.M. (1)
- van Koolwijk, Leonieke M. E. (1)
- van Os, Theo A. M. (1)
- van Rensburg, Elisabeth J. (1)
- van Roozendaal, Kees E. P. (1)
- van Veen, Elke M. (1)
- van der Hoeven, Franciscus (1)
- van der Hout, Annemarie H. (1)
- van der Luijt, Rob B. (1)
- von Kalle, Thekla (1)
- von Paleske, Lisa (1)
- von Polier, Georg G. (1)
- Ösby, Urban (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (7)
- Institut für Humangenetik (4)
- Institut für Theoretische Physik und Astrophysik (4)
- Kinderklinik und Poliklinik (4)
- Medizinische Klinik und Poliklinik II (3)
- Institut für Anatomie und Zellbiologie (2)
- Institut für Psychologie (2)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (2)
- Neurologische Klinik und Poliklinik (2)
- Augenklinik und Poliklinik (1)
Sonstige beteiligte Institutionen
Davis, Lea K. ; Yu, Dongmei ; Keenan, Clare L. ; Gamazon, Eric R. ; Konkashbaev, Anuar I. ; Derks, Eske M. ; Neale, Benjamin M. ; Yang, Jian ; Lee, S. Hong ; Evans, Patrick ; Barr, Cathy L. ; Bellodi, Laura ; Benarroch, Fortu ; Berrio, Gabriel Bedoya ; Bienvenu, Oscar J. ; Bloch, Michael H. ; Blom, Rianne M. ; Bruun, Ruth D. ; Budman, Cathy L. ; Camarena, Beatriz ; Campbell, Desmond ; Cappi, Carolina ; Cardona Silgado, Julio C. ; Cath, Danielle C. ; Cavallini, Maria C. ; Chavira, Denise A. ; Chouinard, Sylvian ; Conti, David V. ; Cook, Edwin H. ; Coric, Vladimir ; Cullen, Bernadette A. ; Deforce, Dieter ; Delorme, Richard ; Dion, Yves ; Edlund, Christopher K. ; Egberts, Karin ; Falkai, Peter ; Fernandez, Thomas V. ; Gallagher, Patience J. ; Garrido, Helena ; Geller, Daniel ; Girard, Simon L. ; Grabe, Hans J. ; Grados, Marco A. ; Greenberg, Benjamin D. ; Gross-Tsur, Varda ; Haddad, Stephen ; Heiman, Gary A. ; Hemmings, Sian M. J. ; Hounie, Ana G. ; Illmann, Cornelia ; Jankovic, Joseph ; Jenike, Micheal A. ; Kennedy, James L. ; King, Robert A. ; Kremeyer, Barbara ; Kurlan, Roger ; Lanzagorta, Nuria ; Leboyer, Marion ; Leckman, James F. ; Lennertz, Leonhard ; Liu, Chunyu ; Lochner, Christine ; Lowe, Thomas L. ; Macciardi, Fabio ; McCracken, James T. ; McGrath, Lauren M. ; Restrepo, Sandra C. Mesa ; Moessner, Rainald ; Morgan, Jubel ; Muller, Heike ; Murphy, Dennis L. ; Naarden, Allan L. ; Ochoa, William Cornejo ; Ophoff, Roel A. ; Osiecki, Lisa ; Pakstis, Andrew J. ; Pato, Michele T. ; Pato, Carlos N. ; Piacentini, John ; Pittenger, Christopher ; Pollak, Yehunda ; Rauch, Scott L. ; Renner, Tobias J. ; Reus, Victor I. ; Richter, Margaret A. ; Riddle, Mark A. ; Robertson, Mary M. ; Romero, Roxana ; Rosàrio, Maria C. ; Rosenberg, David ; Rouleau, Guy A. ; Ruhrmann, Stephan ; Ruiz-Linares, Andreas ; Sampaio, Aline S. ; Samuels, Jack ; Sandor, Paul ; Sheppard, Broke ; Singer, Harvey S. ; Smit, Jan H. ; Stein, Dan J. ; Strengman, E. ; Tischfield, Jay A. ; Valencia Duarte, Ana V. ; Vallada, Homero ; Van Nieuwerburgh, Flip ; Veenstra-VanderWeele, Jeremy ; Walitza, Susanne ; Wang, Ying ; Wendland, Jens R. ; Westenberg, Herman G. M. ; Shugart, Yin Yao ; Miguel, Euripedes C. ; McMahon, William ; Wagner, Michael ; Nicolini, Humberto ; Posthuma, Danielle ; Hanna, Gregory L. ; Heutink, Peter ; Denys, Damiaan ; Arnold, Paul D. ; Oostra, Ben A. ; Nestadt, Gerald ; Freimer, Nelson B. ; Pauls, David L. ; Wray, Naomi R. ; Stewart, S. Evelyn ; Mathews, Carol A. ; Knowles, James A. ; Cox, Nancy J. ; Scharf, Jeremiah M.
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
van Koolwijk, Leonieke M. E. ; Ramdas, Wishal D. ; Ikram, M. Kamran ; Jansonius, Nomdo M. ; Pasutto, Francesca ; Hys, Pirro G. ; Macgregor, Stuart ; Janssen, Sarah F. ; Hewitt, Alex W. ; Viswanathan, Ananth C. ; ten Brink, Jacoline B. ; Hosseini, S. Mohsen ; Amin, Najaf ; Despriet, Dominiek D. G. ; Willemse-Assink, Jacqueline J. M. ; Kramer, Rogier ; Rivadeneira, Fernando ; Struchalin, Maksim ; Aulchenko, Yurii S. ; Weisschuh, Nicole ; Zenkel, Matthias ; Mardin, Christian Y. ; Gramer, Eugen ; Welge-Lüssen, Ulrich ; Montgomery, Grant W. ; Carbonaro, Francis ; Young, Terri L. ; Bellenguez, Céline ; McGuffin, Peter ; Foster, Paul J. ; Topouzis, Fotis ; Mitchell, Paul ; Wang, Jie Jin ; Wong, Tien Y. ; Czudowska, Monika A. ; Hofman, Albert ; Uitterlinden, Andre G. ; Wolfs, Roger C. W. ; de Jong, Paulus T. V. M. ; Oostra, Ben A. ; Paterson, Andrew D. ; Mackey, David A. ; Bergen, Arthur A. B. ; Reis, Andre ; Hammond, Christopher J. ; Vingerling, Johannes R. ; Lemij, Hans G. ; Klaver, Caroline C. W. ; van Duijn, Cornelia M.
Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4 x 10\(^{-8}\)), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6 x 10\(^{-8}\)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4 x 10\(^{-2}\) for rs11656696 and p = 9.1 x 10\(^{-4}\) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.
An expanded evaluation of protein function prediction methods shows an improvement in accuracy
(2016)
Jiang, Yuxiang ; Oron, Tal Ronnen ; Clark, Wyatt T. ; Bankapur, Asma R. ; D'Andrea, Daniel ; Lepore, Rosalba ; Funk, Christopher S. ; Kahanda, Indika ; Verspoor, Karin M. ; Ben-Hur, Asa ; Koo, Da Chen Emily ; Penfold-Brown, Duncan ; Shasha, Dennis ; Youngs, Noah ; Bonneau, Richard ; Lin, Alexandra ; Sahraeian, Sayed M. E. ; Martelli, Pier Luigi ; Profiti, Giuseppe ; Casadio, Rita ; Cao, Renzhi ; Zhong, Zhaolong ; Cheng, Jianlin ; Altenhoff, Adrian ; Skunca, Nives ; Dessimoz, Christophe ; Dogan, Tunca ; Hakala, Kai ; Kaewphan, Suwisa ; Mehryary, Farrokh ; Salakoski, Tapio ; Ginter, Filip ; Fang, Hai ; Smithers, Ben ; Oates, Matt ; Gough, Julian ; Törönen, Petri ; Koskinen, Patrik ; Holm, Liisa ; Chen, Ching-Tai ; Hsu, Wen-Lian ; Bryson, Kevin ; Cozzetto, Domenico ; Minneci, Federico ; Jones, David T. ; Chapman, Samuel ; BKC, Dukka ; Khan, Ishita K. ; Kihara, Daisuke ; Ofer, Dan ; Rappoport, Nadav ; Stern, Amos ; Cibrian-Uhalte, Elena ; Denny, Paul ; Foulger, Rebecca E. ; Hieta, Reija ; Legge, Duncan ; Lovering, Ruth C. ; Magrane, Michele ; Melidoni, Anna N. ; Mutowo-Meullenet, Prudence ; Pichler, Klemens ; Shypitsyna, Aleksandra ; Li, Biao ; Zakeri, Pooya ; ElShal, Sarah ; Tranchevent, Léon-Charles ; Das, Sayoni ; Dawson, Natalie L. ; Lee, David ; Lees, Jonathan G. ; Sillitoe, Ian ; Bhat, Prajwal ; Nepusz, Tamás ; Romero, Alfonso E. ; Sasidharan, Rajkumar ; Yang, Haixuan ; Paccanaro, Alberto ; Gillis, Jesse ; Sedeño-Cortés, Adriana E. ; Pavlidis, Paul ; Feng, Shou ; Cejuela, Juan M. ; Goldberg, Tatyana ; Hamp, Tobias ; Richter, Lothar ; Salamov, Asaf ; Gabaldon, Toni ; Marcet-Houben, Marina ; Supek, Fran ; Gong, Qingtian ; Ning, Wei ; Zhou, Yuanpeng ; Tian, Weidong ; Falda, Marco ; Fontana, Paolo ; Lavezzo, Enrico ; Toppo, Stefano ; Ferrari, Carlo ; Giollo, Manuel ; Piovesan, Damiano ; Tosatto, Silvio C. E. ; del Pozo, Angela ; Fernández, José M. ; Maietta, Paolo ; Valencia, Alfonso ; Tress, Michael L. ; Benso, Alfredo ; Di Carlo, Stefano ; Politano, Gianfranco ; Savino, Alessandro ; Rehman, Hafeez Ur ; Re, Matteo ; Mesiti, Marco ; Valentini, Giorgio ; Bargsten, Joachim W. ; van Dijk, Aalt D. J. ; Gemovic, Branislava ; Glisic, Sanja ; Perovic, Vladmir ; Veljkovic, Veljko ; Almeida-e-Silva, Danillo C. ; Vencio, Ricardo Z. N. ; Sharan, Malvika ; Vogel, Jörg ; Kansakar, Lakesh ; Zhang, Shanshan ; Vucetic, Slobodan ; Wang, Zheng ; Sternberg, Michael J. E. ; Wass, Mark N. ; Huntley, Rachael P. ; Martin, Maria J. ; O'Donovan, Claire ; Robinson, Peter N. ; Moreau, Yves ; Tramontano, Anna ; Babbitt, Patricia C. ; Brenner, Steven E. ; Linial, Michal ; Orengo, Christine A. ; Rost, Burkhard ; Greene, Casey S. ; Mooney, Sean D. ; Friedberg, Iddo ; Radivojac, Predrag ; Veljkovic, Nevena
Background
A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.
Results
We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.
Conclusions
The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.
Schmidt, Thomas S. B. ; Hayward, Matthew R. ; Coelho, Luiis P. ; Li, Simone S. ; Costea, Paul I. ; Voigt, Anita Y. ; Wirbel, Jakob ; Maistrenko, Oleksandr M. ; Alves, Renato J. C. ; Bergsten, Emma ; de Beaufort, Carine ; Sobhani, Iradj ; Heintz-Buschart, Anna ; Sunagawa, Shinichi ; Zeller, Georg ; Wilmes, Paul ; Bork, Peer
The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Ferreira, Manuel A. ; Gamazon, Eric R. ; Al-Ejeh, Fares ; Aittomäki, Kristiina ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arason, Adalgeir ; Arndt, Volker ; Aronson, Kristan J. ; Arun, Banu K. ; Asseryanis, Ella ; Azzollini, Jacopo ; Balmaña, Judith ; Barnes, Daniel R. ; Barrowdale, Daniel ; Beckmann, Matthias W. ; Behrens, Sabine ; Benitez, Javier ; Bermisheva, Marina ; Bialkowska, Katarzyna ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bolla, Manjeet K. ; Borg, Ake ; Brauch, Hiltrud ; Brenner, Hermann ; Broeks, Annegien ; Burwinkel, Barbara ; Caldés, Trinidad ; Caligo, Maria A. ; Campa, Daniele ; Campbell, Ian ; Canzian, Federico ; Carter, Jonathan ; Carter, Brian D. ; Castelao, Jose E. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Christiansen, Hans ; Chung, Wendy K. ; Claes, Kathleen B. M. ; Clarke, Christine L. ; Couch, Fergus J. ; Cox, Angela ; Cross, Simon S. ; Czene, Kamila ; Daly, Mary B. ; de la Hoya, Miguel ; Dennis, Joe ; Devilee, Peter ; Diez, Orland ; Dörk, Thilo ; Dunning, Alison M. ; Dwek, Miriam ; Eccles, Diana M. ; Ejlertsen, Bent ; Ellberg, Carolina ; Engel, Christoph ; Eriksson, Mikael ; Fasching, Peter A. ; Fletcher, Olivia ; Flyger, Henrik ; Friedman, Eitan ; Frost, Debra ; Gabrielson, Marike ; Gago-Dominguez, Manuela ; Ganz, Patricia A. ; Gapstur, Susan M. ; Garber, Judy ; García-Closas, Montserrat ; García-Sáenz, José A. ; Gaudet, Mia M. ; Giles, Graham G. ; Glendon, Gord ; Godwin, Andrew K. ; Goldberg, Mark S. ; Goldgar, David E. ; González-Neira, Anna ; Greene, Mark H. ; Gronwald, Jacek ; Guenél, Pascal ; Haimann, Christopher A. ; Hall, Per ; Hamann, Ute ; He, Wei ; Heyworth, Jane ; Hogervorst, Frans B. L. ; Hollestelle, Antoinette ; Hoover, Robert N. ; Hopper, John L. ; Hulick, Peter J. ; Humphreys, Keith ; Imyanitov, Evgeny N. ; Isaacs, Claudine ; Jakimovska, Milena ; Jakubowska, Anna ; James, Paul A. ; Janavicius, Ramunas ; Jankowitz, Rachel C. ; John, Esther M. ; Johnson, Nichola ; Joseph, Vijai ; Karlan, Beth Y. ; Khusnutdinova, Elza ; Kiiski, Johanna I. ; Ko, Yon-Dschun ; Jones, Michael E. ; Konstantopoulou, Irene ; Kristensen, Vessela N. ; Laitman, Yael ; Lambrechts, Diether ; Lazaro, Conxi ; Leslie, Goska ; Lester, Jenny ; Lesueur, Fabienne ; Lindström, Sara ; Long, Jirong ; Loud, Jennifer T. ; Lubiński, Jan ; Makalic, Enes ; Mannermaa, Arto ; Manoochehri, Mehdi ; Margolin, Sara ; Maurer, Tabea ; Mavroudis, Dimitrios ; McGuffog, Lesley ; Meindl, Alfons ; Menon, Usha ; Michailidou, Kyriaki ; Miller, Austin ; Montagna, Marco ; Moreno, Fernando ; Moserle, Lidia ; Mulligan, Anna Marie ; Nathanson, Katherine L. ; Neuhausen, Susan L. ; Nevanlinna, Heli ; Nevelsteen, Ines ; Nielsen, Finn C. ; Nikitina-Zake, Liene ; Nussbaum, Robert L. ; Offit, Kenneth ; Olah, Edith ; Olopade, Olufunmilayo I. ; Olsson, Håkan ; Osorio, Ana ; Papp, Janos ; Park-Simon, Tjoung-Won ; Parsons, Michael T. ; Pedersen, Inge Sokilde ; Peixoto, Ana ; Peterlongo, Paolo ; Pharaoh, Paul D. P. ; Plaseska-Karanfilska, Dijana ; Poppe, Bruce ; Presneau, Nadege ; Radice, Paolo ; Rantala, Johanna ; Rennert, Gad ; Risch, Harvey A. ; Saloustros, Emmanouil ; Sanden, Kristin ; Sawyer, Elinor J. ; Schmidt, Marjanka K. ; Schmutzler, Rita K. ; Sharma, Priyanka ; Shu, Xiao-Ou ; Simard, Jaques ; Singer, Christian F. ; Soucy, Penny ; Southey, Melissa C. ; Spinelli, John J. ; Spurdle, Amanda B. ; Stone, Jennifer ; Swerdlow, Anthony J. ; Tapper, William J. ; Taylor, Jack A. ; Teixeira, Manuel R. ; Terry, Mary Beth ; Teulé, Alex ; Thomassen, Mads ; Thöne, Kathrin ; Thull, Darcy L. ; Tischkowitz, Marc ; Toland, Amanda E. ; Torres, Diana ; Truong, Thérèse ; Tung, Nadine ; Vachon, Celine M. ; van Asperen, Christi J. ; van den Ouweland, Ans M. W. ; van Rensburg, Elizabeth J. ; Vega, Ana ; Viel, Alexandra ; Wang, Qin ; Wappenschmidt, Barbara ; Weitzel, Jeffrey N. ; Wendt, Camilla ; Winqvist, Robert ; Yang, Xiaohong R. ; Yannoukakos, Drakoulis ; Ziogas, Argyrios ; Kraft, Peter ; Antoniou, Antonis C. ; Zheng, Wei ; Easton, Douglas F. ; Milne, Roger L. ; Beesley, Jonathan ; Chenevix-Trench, Georgia
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
This study examined the impact of three clinical psychological variables (non-pathological levels of depression and anxiety, as well as experimentally manipulated mood) on fat and taste perception in healthy subjects. After a baseline orosensory evaluation, ‘sad’, ‘happy’ and ‘neutral’ video clips were presented to induce corresponding moods in eighty participants. Following mood manipulation, subjects rated five different oral stimuli, appearing sweet, umami, sour, bitter, fatty, which were delivered at five different concentrations each. Depression levels were assessed with Beck’s Depression Inventory (BDI) and anxiety levels were assessed via the Spielberger’s STAI-trait and state questionnaire. Overall, subjects were able to track the concentrations of the stimuli correctly, yet depression level affected taste ratings. First, depression scores were positively correlated with sucrose ratings. Second, subjects with depression scores above the sample median rated sucrose and quinine as more intense after mood induction (positive, negative and neutral). Third and most important, the group with enhanced depression scores did not rate low and high fat stimuli differently after positive or negative mood induction, whereas, during baseline or during the non-emotional neutral condition they rated the fat intensity as increasing with concentration. Consistent with others’ prior observations we also found that sweet and bitter stimuli at baseline were rated as more intense by participants with higher anxiety scores and that after positive and negative mood induction, citric acid was rated as stronger tasting compared to baseline. The observation that subjects with mild subclinical depression rated low and high fat stimuli similarly when in positive or negative mood is novel and likely has potential implications for unhealthy eating patterns. This deficit may foster unconscious eating of fatty foods in sub-clinical mildly depressed populations.
Iyengar, Sudha K. ; Sedor, John R. ; Freedman, Barry I. ; Kao, W. H. Linda ; Kretzler, Matthias ; Keller, Benjamin J. ; Abboud, Hanna E. ; Adler, Sharon G. ; Best, Lyle G. ; Bowden, Donald W. ; Burlock, Allison ; Chen, Yii-Der Ida ; Cole, Shelley A. ; Comeau, Mary E. ; Curtis, Jeffrey M. ; Divers, Jasmin ; Drechsler, Christiane ; Duggirala, Ravi ; Elston, Robert C. ; Guo, Xiuqing ; Huang, Huateng ; Hoffmann, Michael Marcus ; Howard, Barbara V. ; Ipp, Eli ; Kimmel, Paul L. ; Klag, Michael J. ; Knowler, William C. ; Kohn, Orly F. ; Leak, Tennille S. ; Leehey, David J. ; Li, Man ; Malhotra, Alka ; März, Winfried ; Nair, Viji ; Nelson, Robert G. ; Nicholas, Susanne B. ; O’Brien, Stephen J. ; Pahl, Madeleine V. ; Parekh, Rulan S. ; Pezzolesi, Marcus G. ; Rasooly, Rebekah S. ; Rotimi, Charles N. ; Rotter, Jerome I. ; Schelling, Jeffrey R. ; Seldin, Michael F. ; Shah, Vallabh O. ; Smiles, Adam M. ; Smith, Michael W. ; Taylor, Kent D. ; Thameem, Farook ; Thornley-Brown, Denyse P. ; Truitt, Barbara J. ; Wanner, Christoph ; Weil, E. Jennifer ; Winkler, Cheryl A. ; Zager, Philip G. ; Igo, Jr, Robert P. ; Hanson, Robert L. ; Langefeld, Carl D.
Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10\(^{−9}\)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10\(^{−8}\)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.
Couch, Fergus J. ; Wang, Xianshu ; McGuffog, Lesley ; Lee, Andrew ; Olswold, Curtis ; Kuchenbaecker, Karoline B. ; Soucy, Penny ; Fredericksen, Zachary ; Barrowdale, Daniel ; Dennis, Joe ; Gaudet, Mia M. ; Dicks, Ed ; Kosel, Matthew ; Healey, Sue ; Sinilnikova, Olga M. ; Lee, Adam ; Bacot, Françios ; Vincent, Daniel ; Hogervorst, Frans B. L. ; Peock, Susan ; Stoppa-Lyonnet, Dominique ; Jakubowska, Anna ; Radice, Paolo ; Schmutzler, Rita Katharina ; Domchek, Susan M. ; Piedmonte, Marion ; Singer, Christian F. ; Friedman, Eitan ; Thomassen, Mads ; Hansen, Thomas V. O. ; Neuhausen, Susan L. ; Szabo, Csilla I. ; Blanco, Ingnacio ; Greene, Mark H. ; Karlan, Beth Y. ; Garber, Judy ; Phelan, Catherine M. ; Weitzel, Jeffrey N. ; Montagna, Marco ; Olah, Edith ; Andrulis, Irene L. ; Godwin, Andrew K. ; Yannoukakos, Drakoulis ; Goldgar, David E. ; Caldes, Trinidad ; Nevanlinna, Heli ; Osorio, Ana ; Terry, Mary Beth ; Daly, Mary B. ; van Rensburg, Elisabeth J. ; Hamann, Ute ; Ramus, Susan J. ; Toland, Amanda Ewart ; Caligo, Maria A. ; Olopade, Olufunmilayo I. ; Tung, Nadine ; Claes, Kathleen ; Beattie, Mary S. ; Southey, Melissa C. ; Imyanitov, Evgeny N. ; Tischkowitz, Marc ; Janavicius, Ramunas ; John, Esther M. ; Kwong, Ava ; Diez, Orland ; Kwong, Ava ; Balmaña, Judith ; Barkardottir, Rosa B. ; Arun, Banu K. ; Rennert, Gad ; Teo, Soo-Hwang ; Ganz, Patricia A. ; Campbell, Ian ; van der Hout, Annemarie H. ; van Deurzen, Carolien H. M. ; Seynaeve, Caroline ; Garcia, Encarna B. Gómez ; van Leeuwen, Flora E. ; Meijers-Heijboer, Hanne E. J. ; Gille, Johannes J. P. ; Ausems, Magreet G. E. M. ; Blok, Marinus J. ; Ligtenberg, Marjolinjin J. L. ; Rookus, Matti A. ; Devilee, Peter ; Verhoef, Senno ; van Os, Theo A. M. ; Wijnen, Juul T. ; Frost, Debra ; Ellis, Steve ; Fineberg, Elena ; Platte, Radke ; Evans, D. Gareth ; Izatt, Luise ; Eeles, Rosalind A. ; Adlard, Julian ; Eccles, Diana M. ; Cook, Jackie ; Brewer, Carole ; Douglas, Fiona ; Hodgson, Shirley ; Morrison, Patrick J. ; Side, Lucy E. ; Donaldson, Alan ; Houghton, Catherine ; Rogers, Mark T. ; Dorkins, Huw ; Eason, Jacqueline ; Gregory, Helen ; McCann, Emma ; Murray, Alex ; Calender, Alain ; Hardouin, Agnès ; Berthet, Pascaline ; Delnatte, Capucine ; Nogues, Catherine ; Lasset, Christine ; Houdayer, Claude ; Leroux,, Dominique ; Rouleau, Etienne ; Prieur, Fabienne ; Damiola, Francesca ; Sobol, Hagay ; Coupier, Isabelle ; Venat-Bouvet, Laurence ; Castera, Laurent ; Gauthier-Villars, Marion ; Léoné, Mélanie ; Pujol, Pascal ; Mazoyer, Sylvie ; Bignon, Yves-Jean ; Zlowocka-Perlowska, Elzbieta ; Gronwald, Jacek ; Lubinski,, Jan ; Durda, Katarzyna ; Jaworska, Katarzyna ; Huzarski, Tomasz ; Spurdle, Amanda B. ; Viel, Alessandra ; Peissel, Bernhard ; Bonanni, Bernardo ; Melloni, Guilia ; Ottini, Laura ; Papi, Laura ; Varesco, Liliana ; Tibiletti, Maria Grazia ; Peterlongo, Paolo ; Volorio, Sara ; Manoukian, Siranoush ; Pensotti, Valeria ; Arnold, Norbert ; Engel, Christoph ; Deissler, Helmut ; Gadzicki, Dorothea ; Gehrig, Andrea ; Kast, Karin ; Rhiem, Kerstin ; Meindl, Alfons ; Niederacher, Dieter ; Ditsch, Nina ; Plendl, Hansjoerg ; Preisler-Adams, Sabine ; Engert, Stefanie ; Sutter, Christian ; Varon-Mateeva, Raymenda ; Wappenschmidt, Barbara ; Weber, Bernhard H. F. ; Arver, Brita ; Stenmark-Askmalm, Marie ; Loman, Niklas ; Rosenquist, Richard ; Einbeigi, Zakaria ; Nathanson, Katherine L. ; Rebbeck, Timothy R. ; Blank, Stephanie V. ; Cohn, David E. ; Rodriguez, Gustavo C. ; Small, Laurie ; Friedlander, Michael ; Bae-Jump, Victoria L. ; Fink-Retter, Anneliese ; Rappaport, Christine ; Gschwantler-Kaulich, Daphne ; Pfeiler, Georg ; Tea, Muy-Kheng ; Lindor, Noralane M. ; Kaufman, Bella ; Paluch, Shani Shimon ; Laitman, Yael ; Skytte, Anne-Bine ; Gerdes, Anne-Marie ; Pedersen, Inge Sokilde ; Moeller, Sanne Traasdahl ; Kruse, Torben A. ; Jensen, Uffe Birk ; Vijai, Joseph ; Sarrel, Kara ; Robson, Mark ; Kauff, Noah ; Mulligan, Anna Marie ; Glendon, Gord ; Ozcelik, Hilmi ; Ejlertsen, Bent ; Nielsen, Finn C. ; Jønson, Lars ; Andersen, Mette K. ; Ding, Yuan Chun ; Steele, Linda ; Foretova, Lenka ; Teulé, Alex ; Lazaro, Conxi ; Brunet, Joan ; Pujana, Miquel Angel ; Mai, Phuong L. ; Loud, Jennifer T. ; Walsh, Christine ; Lester, Jenny ; Orsulic, Sandra ; Narod, Steven A. ; Herzog, Josef ; Sand, Sharon R. ; Tognazzo, Silvia ; Agata, Simona ; Vaszko, Tibor ; Weaver, Joellen ; Stravropoulou, Alexandra V. ; Buys, Saundra S. ; Romero, Atocha ; de la Hoya, Miguel ; Aittomäki, Kristiina ; Muranen, Taru A. ; Duran, Mercedes ; Chung, Wendy K. ; Lasa, Adriana ; Dorfling, Cecilia M. ; Miron, Alexander ; Benitez, Javier ; Senter, Leigha ; Huo, Dezheng ; Chan, Salina B. ; Sokolenko, Anna P. ; Chiquette, Jocelyne ; Tihomirova, Laima ; Friebel, Tara M. ; Agnarsson, Bjarne A. ; Lu, Karen H. ; Lejbkowicz, Flavio ; James, Paul A. ; Hall, Per ; Dunning, Alison M. ; Tessier, Daniel ; Cunningham, Julie ; Slager, Susan L. ; Chen, Wang ; Hart, Steven ; Stevens, Kristen ; Simard, Jacques ; Pastinen, Tomi ; Pankratz, Vernon S. ; Offit, Kenneth ; Easton, Douglas F. ; Chenevix-Trench, Georgia ; Antoniou, Antonis C.
BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
Deeb, Wissam ; Giordano, James J. ; Rossi, Peter J. ; Mogilner, Alon Y. ; Gunduz, Aysegul ; Judy, Jack W. ; Klassen, Bryan T. ; Butson, Christopher R. ; Van Horne, Craig ; Deny, Damiaan ; Dougherty, Darin D. ; Rowell, David ; Gerhardt, Greg A. ; Smith, Gwenn S. ; Ponce, Francisco A. ; Walker, Harrison C. ; Bronte-Stewart, Helen M. ; Mayberg, Helen S. ; Chizeck, Howard J. ; Langevin, Jean-Philippe ; Volkmann, Jens ; Ostrem, Jill L. ; Shute, Jonathan B. ; Jimenez-Shahed, Joohi ; Foote, Kelly D. ; Wagle Shukla, Aparna ; Rossi, Marvin A. ; Oh, Michael ; Pourfar, Michael ; Rosenberg, Paul B. ; Silburn, Peter A. ; de Hemptine, Coralie ; Starr, Philip A. ; Denison, Timothy ; Akbar, Umer ; Grill, Warren M. ; Okun, Michael S.
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.
Bäuerlein, Carina A. ; Riedel, Simone S. ; Baker, Jeanette ; Brede, Christian ; Jordán Garrote, Ana-Laura ; Chopra, Martin ; Ritz, Miriam ; Beilhack, Georg F. ; Schulz, Stephan ; Zeiser, Robert ; Schlegel, Paul G. ; Einsele, Hermann ; Negrin, Robert S. ; Beilhack, Andreas
Background
Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention.
Methods
Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles.
Results
We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated α4β7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD.
Conclusions
Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention.