@article{SilvestriBarrowdaleMulliganetal.2016, author = {Silvestri, Valentina and Barrowdale, Daniel and Mulligan, Anna Marie and Neuhausen, Susan L. and Fox, Stephen and Karlan, Beth Y. and Mitchell, Gillian and James, Paul and Thull, Darcy L. and Zorn, Kristin K. and Carter, Natalie J. and Nathanson, Katherine L. and Domchek, Susan M. and Rebbeck, Timothy R. and Ramus, Susan J. and Nussbaum, Robert L. and Olopade, Olufunmilayo I. and Rantala, Johanna and Yoon, Sook-Yee and Caligo, Maria A. and Spugnesi, Laura and Bojesen, Anders and Pedersen, Inge Sokilde and Thomassen, Mads and Jensen, Uffe Birk and Toland, Amanda Ewart and Senter, Leigha and Andrulis, Irene L. and Glendon, Gord and Hulick, Peter J. and Imyanitov, Evgeny N. and Greene, Mark H. and Mai, Phuong L. and Singer, Christian F. and Rappaport-Fuerhauser, Christine and Kramer, Gero and Vijai, Joseph and Offit, Kenneth and Robson, Mark and Lincoln, Anne and Jacobs, Lauren and Machackova, Eva and Foretova, Lenka and Navratilova, Marie and Vasickova, Petra and Couch, Fergus J. and Hallberg, Emily and Ruddy, Kathryn J. and Sharma, Priyanka and Kim, Sung-Won and Teixeira, Manuel R. and Pinto, Pedro and Montagna, Marco and Matricardi, Laura and Arason, Adalgeir and Johannsson, Oskar Th and Barkardottir, Rosa B. and Jakubowska, Anna and Lubinski, Jan and Izquierdo, Angel and Pujana, Miguel Angel and Balma{\~n}a, Judith and Diez, Orland and Ivady, Gabriella and Papp, Janos and Olah, Edith and Kwong, Ava and Nevanlinna, Heli and Aittom{\"a}ki, Kristiina and Segura, Pedro Perez and Caldes, Trinidad and Van Maerken, Tom and Poppe, Bruce and Claes, Kathleen B. M. and Isaacs, Claudine and Elan, Camille and Lasset, Christine and Stoppa-Lyonnet, Dominique and Barjhoux, Laure and Belotti, Muriel and Meindl, Alfons and Gehrig, Andrea and Sutter, Christian and Engel, Christoph and Niederacher, Dieter and Steinemann, Doris and Hahnen, Eric and Kast, Karin and Arnold, Norbert and Varon-Mateeva, Raymonda and Wand, Dorothea and Godwin, Andrew K. and Evans, D. Gareth and Frost, Debra and Perkins, Jo and Adlard, Julian and Izatt, Louise and Platte, Radka and Eeles, Ros and Ellis, Steve and Hamann, Ute and Garber, Judy and Fostira, Florentia and Fountzilas, George and Pasini, Barbara and Giannini, Giuseppe and Rizzolo, Piera and Russo, Antonio and Cortesi, Laura and Papi, Laura and Varesco, Liliana and Palli, Domenico and Zanna, Ines and Savarese, Antonella and Radice, Paolo and Manoukian, Siranoush and Peissel, Bernard and Barile, Monica and Bonanni, Bernardo and Viel, Alessandra and Pensotti, Valeria and Tommasi, Stefania and Peterlongo, Paolo and Weitzel, Jeffrey N. and Osorio, Ana and Benitez, Javier and McGuffog, Lesley and Healey, Sue and Gerdes, Anne-Marie and Ejlertsen, Bent and Hansen, Thomas V. O. and Steele, Linda and Ding, Yuan Chun and Tung, Nadine and Janavicius, Ramunas and Goldgar, David E. and Buys, Saundra S. and Daly, Mary B. and Bane, Anita and Terry, Mary Beth and John, Esther M. and Southey, Melissa and Easton, Douglas F. and Chenevix-Trench, Georgia and Antoniou, Antonis C. and Ottini, Laura}, title = {Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2}, series = {Breast Cancer Research}, volume = {18}, journal = {Breast Cancer Research}, number = {15}, doi = {10.1186/s13058-016-0671-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164769}, year = {2016}, abstract = {Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10-5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 \% confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 \% CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10-12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.}, language = {en} } @article{DoerkPeterlongoMannermaaetal.2019, author = {D{\"o}rk, Thilo and Peterlongo, Peter and Mannermaa, Arto and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Ahearn, Thomas and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Augustinsson, Annelie and Beane Freeman, Laura E. and Beckmann, Matthias W. and Beeghly-Fadiel, Alicia and Behrens, Sabine and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Brauch, Hiltrud and Brenner, Hermann and Burwinkel, Barbara and Canzian, Federico and Chan, Tsun L. and Chang-Claude, Jenny and Chanock, Stephen J. and Choi, Ji-Yeob and Christiansen, Hans and Clarke, Christine L. and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and dos-Santos-Silva, Isabel and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif B. and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter A. and Figueroa, Jonine and Flyger, Henrik and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and Gao, Chi and Gapstur, Susan M. and Garc{\´i}a-Closas, Montserrat and Garc{\´i}a-S{\´a}enz, Jos{\´e} A. and Gaudet, Mia M. and Giles, Graham G. and Goldberg, Mark S. and Goldgar, David E. and Guen{\´e}l, Pascal and Haeberle, Lothar and Haimann, Christopher A. and H{\aa}kansson, Niclas and Hall, Per and Hamann, Ute and Hartman, Mikael and Hauke, Jan and Hein, Alexander and Hillemanns, Peter and Hogervorst, Frans B. L. and Hooning, Maartje J. and Hopper, John L. and Howell, Tony and Huo, Dezheng and Ito, Hidemi and Iwasaki, Motoki and Jakubowska, Anna and Janni, Wolfgang and John, Esther M. and Jung, Audrey and Kaaks, Rudolf and Kang, Daehee and Kapoor, Pooja Middha and Khusnutdinova, Elza and Kim, Sung-Won and Kitahara, Cari M. and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N. and Kwong, Ava and Lambrechts, Diether and Le Marchand, Loic and Li, Jingmei and Lindstr{\"o}m, Sara and Linet, Martha and Lo, Wing-Yee and Long, Jirong and Lophatananon, Artitaya and Lubiński, Jan and Manoochehri, Mehdi and Manoukian, Siranoush and Margolin, Sara and Martinez, Elena and Matsuo, Keitaro and Mavroudis, Dimitris and Meindl, Alfons and Menon, Usha and Milne, Roger L. and Mohd Taib, Nur Aishah and Muir, Kenneth and Mulligan, Anna Marie and Neuhausen, Susan L. and Nevanlinna, Heli and Neven, Patrick and Newman, William G. and Offit, Kenneth and Olopade, Olufunmilayo I. and Olshan, Andrew F. and Olson, Janet E. and Olsson, H{\aa}kan and Park, Sue K. and Park-Simon, Tjoung-Won and Peto, Julian and Plaseska-Karanfilska, Dijana and Pohl-Rescigno, Esther and Presneau, Nadege and Rack, Brigitte and Radice, Paolo and Rashid, Muhammad U. and Rennert, Gad and Rennert, Hedy S. and Romero, Atocha and Ruebner, Matthias and Saloustros, Emmanouil and Schmidt, Marjanka K. and Schmutzler, Rita K. and Schneider, Michael O. and Schoemaker, Minouk J. and Scott, Christopher and Shen, Chen-Yang and Shu, Xiao-Ou and Simard, Jaques and Slager, Susan and Smichkoska, Snezhana and Southey, Melissa C. and Spinelli, John J. and Stone, Jennifer and Surowy, Harald and Swerdlow, Anthony J. and Tamimi, Rulla M. and Tapper, William J. and Teo, Soo H. and Terry, Mary Beth and Toland, Amanda E. and Tollenaar, Rob A. E. M. and Torres, Diana and Torres-Mej{\´i}a, Gabriela and Troester, Melissa A. and Truong, Th{\´e}r{\`e}se and Tsugane, Shoichiro and Untch, Michael and Vachon, Celine M. and van den Ouweland, Ans M. W. and van Veen, Elke M. and Vijai, Joseph and Wendt, Camilla and Wolk, Alicja and Yu, Jyh-Cherng and Zheng, Wei and Ziogas, Argyrios and Ziv, Elad and Dunnig, Alison and Pharaoh, Paul D. P. and Schindler, Detlev and Devilee, Peter and Easton, Douglas F.}, title = {Two truncating variants in FANCC and breast cancer risk}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, organization = {ABCTB Investigators, NBCS Collaborators}, doi = {10.1038/s41598-019-48804-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222838}, year = {2019}, abstract = {Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95\%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.}, language = {en} } @article{GeorgievChaoCastroetal.2020, author = {Georgiev, Kostadin B. and Chao, Anne and Castro, Jorge and Chen, Yan-Han and Choi, Chang-Yong and Fontaine, Joseph B. and Hutto, Richard L. and Lee, Eun-Jae and M{\"u}ller, J{\"o}rg and Rost, Josep and Żmihorski, Michal and Thorn, Simon}, title = {Salvage logging changes the taxonomic, phylogenetic and functional successional trajectories of forest bird communities}, series = {Journal of Applied Ecology}, volume = {57}, journal = {Journal of Applied Ecology}, number = {6}, doi = {10.1111/1365-2664.13599}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214887}, pages = {1103 -- 1112}, year = {2020}, abstract = {Salvage logging following natural disturbances may alter the natural successional trajectories of biological communities by affecting the occurrences of species, functional groups and evolutionary lineages. However, few studies have examined whether dissimilarities between bird communities of salvaged and unsalvaged forests are more pronounced for rare species, functional groups and evolutionary lineages than for their more common counterparts. We compiled data on breeding bird assemblages from nine study areas in North America, Europe and Asia, covering a 17-year period following wildfire or windstorm disturbances and subsequent salvage logging. We tested whether dissimilarities based on non-shared species, functional groups and evolutionary lineages (a) decreased or increased over time and (b) the responses of rare, common and dominant species varied, by using a unified statistical framework based on Hill numbers and null models. We found that dissimilarities between bird communities caused by salvage logging persisted over time for rare, common and dominant species, evolutionary lineages and for rare functional groups. Dissimilarities of common and dominant functional groups increased 14 years post disturbance. Salvage logging led to significantly larger dissimilarities than expected by chance. Functional dissimilarities between salvaged and unsalvaged sites were lower compared to taxonomic and phylogenetic dissimilarities. In general, dissimilarities were highest for rare, followed by common and dominant species. Synthesis and applications. Our research demonstrates that salvage logging did not decrease dissimilarities of bird communities over time and taxonomic, functional and phylogenetic dissimilarities persisted for over a decade. We recommend resource managers and decision makers to reserve portions of disturbed forest to enable unmanaged post-disturbance succession of bird communities, particularly to conserve rare species found in unsalvaged disturbed forests.}, language = {en} } @article{PostemaHoogmanAmbrosinoetal.2021, author = {Postema, Merel C. and Hoogman, Martine and Ambrosino, Sara and Asherson, Philip and Banaschewski, Tobias and Bandeira, Cibele E. and Baranov, Alexandr and Bau, Claiton H.D. and Baumeister, Sarah and Baur-Streubel, Ramona and Bellgrove, Mark A. and Biederman, Joseph and Bralten, Janita and Brandeis, Daniel and Brem, Silvia and Buitelaar, Jan K. and Busatto, Geraldo F. and Castellanos, Francisco X. and Cercignani, Mara and Chaim-Avancini, Tiffany M. and Chantiluke, Kaylita C. and Christakou, Anastasia and Coghill, David and Conzelmann, Annette and Cubillo, Ana I. and Cupertino, Renata B. and de Zeeuw, Patrick and Doyle, Alysa E. and Durston, Sarah and Earl, Eric A. and Epstein, Jeffery N. and Ethofer, Thomas and Fair, Damien A. and Fallgatter, Andreas J. and Faraone, Stephen V. and Frodl, Thomas and Gabel, Matt C. and Gogberashvili, Tinatin and Grevet, Eugenio H. and Haavik, Jan and Harrison, Neil A. and Hartman, Catharina A. and Heslenfeld, Dirk J. and Hoekstra, Pieter J. and Hohmann, Sarah and H{\o}vik, Marie F. and Jernigan, Terry L. and Kardatzki, Bernd and Karkashadze, Georgii and Kelly, Clare and Kohls, Gregor and Konrad, Kerstin and Kuntsi, Jonna and Lazaro, Luisa and Lera-Miguel, Sara and Lesch, Klaus-Peter and Louza, Mario R. and Lundervold, Astri J. and Malpas, Charles B and Mattos, Paulo and McCarthy, Hazel and Namazova-Baranova, Leyla and Nicolau, Rosa and Nigg, Joel T. and Novotny, Stephanie E. and Oberwelland Weiss, Eileen and O'Gorman Tuura, Ruth L. and Oosterlaan, Jaap and Oranje, Bob and Paloyelis, Yannis and Pauli, Paul and Picon, Felipe A. and Plessen, Kerstin J. and Ramos-Quiroga, J. Antoni and Reif, Andreas and Reneman, Liesbeth and Rosa, Pedro G.P. and Rubia, Katya and Schrantee, Anouk and Schweren, Lizanne J.S. and Seitz, Jochen and Shaw, Philip and Silk, Tim J. and Skokauskas, Norbert and Soliva Vila, Juan C. and Stevens, Michael C. and Sudre, Gustavo and Tamm, Leanne and Tovar-Moll, Fernanda and van Erp, Theo G.M. and Vance, Alasdair and Vilarroya, Oscar and Vives-Gilabert, Yolanda and von Polier, Georg G. and Walitza, Susanne and Yoncheva, Yuliya N. and Zanetti, Marcus V. and Ziegler, Georg C. and Glahn, David C. and Jahanshad, Neda and Medland, Sarah E. and Thompson, Paul M. and Fisher, Simon E. and Franke, Barbara and Francks, Clyde}, title = {Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets}, series = {Journal of Child Psychology and Psychiatry}, volume = {62}, journal = {Journal of Child Psychology and Psychiatry}, number = {10}, doi = {10.1111/jcpp.13396}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239968}, pages = {1202 -- 1219}, year = {2021}, abstract = {Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.}, language = {en} } @article{IslesIngasonLowtheretal.2016, author = {Isles, Anthony R. and Ingason, Andr{\´e}s and Lowther, Chelsea and Walters, James and Gawlick, Micha and St{\"o}ber, Gerald and Rees, Elliott and Martin, Joanna and Little, Rosie B. and Potter, Harry and Georgieva, Lyudmila and Pizzo, Lucilla and Ozaki, Norio and Aleksic, Branko and Kushima, Itaru and Ikeda, Masashi and Iwata, Nakao and Levinson, Douglas F. and Gejman, Pablo V. and Shi, Jianxin and Sanders, Alan R. and Duan, Jubao and Willis, Joseph and Sisodiya, Sanjay and Costain, Gregory and Werge, Thomas M. and Degenhardt, Franziska and Giegling, Ina and Rujescu, Dan and Hreidarsson, Stefan J. and Saemundsen, Evald and Ahn, Joo Wook and Ogilvie, Caroline and Girirajan, Santhosh D. and Stefansson, Hreinn and Stefansson, Kari and O'Donovan, Michael C. and Owen, Michael J. and Bassett, Anne and Kirov, George}, title = {Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders}, series = {PLoS Genetics}, volume = {12}, journal = {PLoS Genetics}, number = {5}, doi = {10.1371/journal.pgen.1005993}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166706}, pages = {e1005993}, year = {2016}, abstract = {Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76\% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033\% compared to 0.0069\% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50\% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally expressed imprinted genes in the contribution of Copy Number Variants (CNVs) at this interval to the incidence of psychotic illness. This work will have tangible benefits for patients with 15q11.2-q13.3 duplications by aiding genetic counseling.}, language = {en} } @article{DavisYuKeenanetal.2013, author = {Davis, Lea K. and Yu, Dongmei and Keenan, Clare L. and Gamazon, Eric R. and Konkashbaev, Anuar I. and Derks, Eske M. and Neale, Benjamin M. and Yang, Jian and Lee, S. Hong and Evans, Patrick and Barr, Cathy L. and Bellodi, Laura and Benarroch, Fortu and Berrio, Gabriel Bedoya and Bienvenu, Oscar J. and Bloch, Michael H. and Blom, Rianne M. and Bruun, Ruth D. and Budman, Cathy L. and Camarena, Beatriz and Campbell, Desmond and Cappi, Carolina and Cardona Silgado, Julio C. and Cath, Danielle C. and Cavallini, Maria C. and Chavira, Denise A. and Chouinard, Sylvian and Conti, David V. and Cook, Edwin H. and Coric, Vladimir and Cullen, Bernadette A. and Deforce, Dieter and Delorme, Richard and Dion, Yves and Edlund, Christopher K. and Egberts, Karin and Falkai, Peter and Fernandez, Thomas V. and Gallagher, Patience J. and Garrido, Helena and Geller, Daniel and Girard, Simon L. and Grabe, Hans J. and Grados, Marco A. and Greenberg, Benjamin D. and Gross-Tsur, Varda and Haddad, Stephen and Heiman, Gary A. and Hemmings, Sian M. J. and Hounie, Ana G. and Illmann, Cornelia and Jankovic, Joseph and Jenike, Micheal A. and Kennedy, James L. and King, Robert A. and Kremeyer, Barbara and Kurlan, Roger and Lanzagorta, Nuria and Leboyer, Marion and Leckman, James F. and Lennertz, Leonhard and Liu, Chunyu and Lochner, Christine and Lowe, Thomas L. and Macciardi, Fabio and McCracken, James T. and McGrath, Lauren M. and Restrepo, Sandra C. Mesa and Moessner, Rainald and Morgan, Jubel and Muller, Heike and Murphy, Dennis L. and Naarden, Allan L. and Ochoa, William Cornejo and Ophoff, Roel A. and Osiecki, Lisa and Pakstis, Andrew J. and Pato, Michele T. and Pato, Carlos N. and Piacentini, John and Pittenger, Christopher and Pollak, Yehunda and Rauch, Scott L. and Renner, Tobias J. and Reus, Victor I. and Richter, Margaret A. and Riddle, Mark A. and Robertson, Mary M. and Romero, Roxana and Ros{\`a}rio, Maria C. and Rosenberg, David and Rouleau, Guy A. and Ruhrmann, Stephan and Ruiz-Linares, Andreas and Sampaio, Aline S. and Samuels, Jack and Sandor, Paul and Sheppard, Broke and Singer, Harvey S. and Smit, Jan H. and Stein, Dan J. and Strengman, E. and Tischfield, Jay A. and Valencia Duarte, Ana V. and Vallada, Homero and Van Nieuwerburgh, Flip and Veenstra-VanderWeele, Jeremy and Walitza, Susanne and Wang, Ying and Wendland, Jens R. and Westenberg, Herman G. M. and Shugart, Yin Yao and Miguel, Euripedes C. and McMahon, William and Wagner, Michael and Nicolini, Humberto and Posthuma, Danielle and Hanna, Gregory L. and Heutink, Peter and Denys, Damiaan and Arnold, Paul D. and Oostra, Ben A. and Nestadt, Gerald and Freimer, Nelson B. and Pauls, David L. and Wray, Naomi R. and Stewart, S. Evelyn and Mathews, Carol A. and Knowles, James A. and Cox, Nancy J. and Scharf, Jeremiah M.}, title = {Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture}, series = {PLoS Genetics}, volume = {9}, journal = {PLoS Genetics}, number = {10}, issn = {1553-7390}, doi = {10.1371/journal.pgen.1003864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127377}, pages = {e1003864}, year = {2013}, abstract = {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.}, language = {en} } @article{WangChenMinevetal.2013, author = {Wang, Huiqiang and Chen, Nanhai G. and Minev, Boris R. and Zimmermann, Martina and Aguilar, Richard J. and Zhang, Qian and Sturm, Julia B. and Fend, Falko and Yu, Yong A. and Cappello, Joseph and Lauer, Ulrich M. and Szalay, Aladar A.}, title = {Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0071105}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130059}, pages = {e71105}, year = {2013}, abstract = {Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.}, language = {en} } @article{PetersHempAppelhansetal.2016, author = {Peters, Marcell K. and Hemp, Andreas and Appelhans, Tim and Behler, Christina and Classen, Alice and Detsch, Florian and Ensslin, Andreas and Ferger, Stefan W. and Frederiksen, Sara B. and Gebert, Frederike and Haas, Michael and Helbig-Bonitz, Maria and Hemp, Claudia and Kindeketa, William J. and Mwangomo, Ephraim and Ngereza, Christine and Otte, Insa and R{\"o}der, Juliane and Rutten, Gemma and Costa, David Schellenberger and Tardanico, Joseph and Zancolli, Giulia and Deckert, J{\"u}rgen and Eardley, Connal D. and Peters, Ralph S. and R{\"o}del, Mark-Oliver and Schleuning, Matthias and Ssymank, Axel and Kakengi, Victor and Zhang, Jie and B{\"o}hning-Gaese, Katrin and Brandl, Roland and Kalko, Elisabeth K.V. and Kleyer, Michael and Nauss, Thomas and Tschapka, Marco and Fischer, Markus and Steffan-Dewenter, Ingolf}, title = {Predictors of elevational biodiversity gradients change from single taxa to the multi-taxa community level}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms13736}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169374}, year = {2016}, abstract = {The factors determining gradients of biodiversity are a fundamental yet unresolved topic in ecology. While diversity gradients have been analysed for numerous single taxa, progress towards general explanatory models has been hampered by limitations in the phylogenetic coverage of past studies. By parallel sampling of 25 major plant and animal taxa along a 3.7 km elevational gradient on Mt. Kilimanjaro, we quantify cross-taxon consensus in diversity gradients and evaluate predictors of diversity from single taxa to a multi-taxa community level. While single taxa show complex distribution patterns and respond to different environmental factors, scaling up diversity to the community level leads to an unambiguous support for temperature as the main predictor of species richness in both plants and animals. Our findings illuminate the influence of taxonomic coverage for models of diversity gradients and point to the importance of temperature for diversification and species coexistence in plant and animal communities.}, language = {en} } @article{MuellerGirardHopfneretal.2016, author = {M{\"u}ller, Stefanie H. and Girard, Simon L. and Hopfner, Franziska and Merner, Nancy D. and Bourassa, Cynthia V. and Lorenz, Delia and Clark, Lorraine N. and Tittmann, Lukas and Soto-Ortolaza, Alexandra I. and Klebe, Stephan and Hallett, Mark and Schneider, Susanne A. and Hodgkinson, Colin A. and Lieb, Wolfgang and Wszolek, Zbigniew K. and Pendziwiat, Manuela and Lorenzo-Betancor, Oswaldo and Poewe, Werner and Ortega-Cubero, Sara and Seppi, Klaus and Rajput, Alex and Hussl, Anna and Rajput, Ali H. and Berg, Daniela and Dion, Patrick A. and Wurster, Isabel and Shulman, Joshua M. and Srulijes, Karin and Haubenberger, Dietrich and Pastor, Pau and Vilari{\~n}o-G{\"u}ell, Carles and Postuma, Ronald B. and Bernard, Genevi{\`e}ve and Ladwig, Karl-Heinz and Dupr{\´e}, Nicolas and Jankovic, Joseph and Strauch, Konstantin and Panisset, Michel and Winkelmann, Juliane and Testa, Claudia M. and Reischl, Eva and Zeuner, Kirsten E. and Ross, Owen A. and Arzberger, Thomas and Chouinard, Sylvain and Deuschl, G{\"u}nther and Louis, Elan D. and Kuhlenb{\"a}umer, Gregor and Rouleau, Guy A.}, title = {Genome-wide association study in essential tremor identifies three new loci}, series = {Brain}, volume = {139}, journal = {Brain}, doi = {10.1093/brain/aww242}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186541}, pages = {3163-3169}, year = {2016}, abstract = {We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.}, language = {en} }