@article{MajounieRentonMoketal.2012, author = {Majounie, Elisa and Renton, Alan E. and Mok, Kin and Dopper, Elise G. P. and Waite, Adrian and Rollinson, Sara and Chi{\`o}, Adriano and Restagno, Gabriella and Nicolaou, Nayia and Simon-Sanchez, Javier and van Swieten, John C. and Abramzon, Yevgeniya and Johnson, Janel O. and Sendtner, Michael and Pamphlett, Roger and Orrell, Richard W. and Mead, Simon and Sidle, Katie C. and Houlden, Henry and Rohrer, Jonathan D. and Morrison, Karen E. and Pall, Hardev and Talbot, Kevin and Ansorge, Olaf and Hernandez, Dena G. and Arepalli, Sampath and Sabatelli, Mario and Mora, Gabriele and Corbo, Massimo and Giannini, Fabio and Calvo, Andrea and Englund, Elisabet and Borghero, Giuseppe and Floris, Gian Luca and Remes, Anne M. and Laaksovirta, Hannu and McCluskey, Leo and Trojanowski, John Q. and Van Deerlin, Vivianna M. and Schellenberg, Gerard D. and Nalls, Michael A. and Drory, Vivian E. and Lu, Chin-Song and Yeh, Tu-Hsueh and Ishiura, Hiroyuki and Takahashi, Yuji and Tsuji, Shoji and Le Ber, Isabelle and Brice, Alexis and Drepper, Carsten and Williams, Nigel and Kirby, Janine and Shaw, Pamela and Hardy, John and Tienari, Pentti J. and Heutink, Peter and Morris, Huw R. and Pickering-Brown, Stuart and Traynor, Bryan J.}, title = {Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study}, series = {The Lancet Neurology}, volume = {11}, journal = {The Lancet Neurology}, doi = {10.1016/S1474-4422(12)70043-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154644}, pages = {323 -- 330}, year = {2012}, abstract = {Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0\%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1\%) of 49 black individuals from the USA, and six (8·3\%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39·3\%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6·0\%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24·8\%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50\% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.}, language = {en} } @article{FerreiraGamazonAlEjehetal.2019, author = {Ferreira, Manuel A. and Gamazon, Eric R. and Al-Ejeh, Fares and Aittom{\"a}ki, Kristiina and Andrulis, Irene L. and Anton-Culver, Hoda and Arason, Adalgeir and Arndt, Volker and Aronson, Kristan J. and Arun, Banu K. and Asseryanis, Ella and Azzollini, Jacopo and Balma{\~n}a, Judith and Barnes, Daniel R. and Barrowdale, Daniel and Beckmann, Matthias W. and Behrens, Sabine and Benitez, Javier and Bermisheva, Marina and Bialkowska, Katarzyna and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Bolla, Manjeet K. and Borg, Ake and Brauch, Hiltrud and Brenner, Hermann and Broeks, Annegien and Burwinkel, Barbara and Cald{\´e}s, Trinidad and Caligo, Maria A. and Campa, Daniele and Campbell, Ian and Canzian, Federico and Carter, Jonathan and Carter, Brian D. and Castelao, Jose E. and Chang-Claude, Jenny and Chanock, Stephen J. and Christiansen, Hans and Chung, Wendy K. and Claes, Kathleen B. M. and Clarke, Christine L. and Couch, Fergus J. and Cox, Angela and Cross, Simon S. and Czene, Kamila and Daly, Mary B. and de la Hoya, Miguel and Dennis, Joe and Devilee, Peter and Diez, Orland and D{\"o}rk, Thilo and Dunning, Alison M. and Dwek, Miriam and Eccles, Diana M. and Ejlertsen, Bent and Ellberg, Carolina and Engel, Christoph and Eriksson, Mikael and Fasching, Peter A. and Fletcher, Olivia and Flyger, Henrik and Friedman, Eitan and Frost, Debra and Gabrielson, Marike and Gago-Dominguez, Manuela and Ganz, Patricia A. and Gapstur, Susan M. and Garber, Judy 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 Glendon, Gord and Godwin, Andrew K. and Goldberg, Mark S. and Goldgar, David E. and Gonz{\´a}lez-Neira, Anna and Greene, Mark H. and Gronwald, Jacek and Guen{\´e}l, Pascal and Haimann, Christopher A. and Hall, Per and Hamann, Ute and He, Wei and Heyworth, Jane and Hogervorst, Frans B. L. and Hollestelle, Antoinette and Hoover, Robert N. and Hopper, John L. and Hulick, Peter J. and Humphreys, Keith and Imyanitov, Evgeny N. and Isaacs, Claudine and Jakimovska, Milena and Jakubowska, Anna and James, Paul A. and Janavicius, Ramunas and Jankowitz, Rachel C. and John, Esther M. and Johnson, Nichola and Joseph, Vijai and Karlan, Beth Y. and Khusnutdinova, Elza and Kiiski, Johanna I. and Ko, Yon-Dschun and Jones, Michael E. and Konstantopoulou, Irene and Kristensen, Vessela N. and Laitman, Yael and Lambrechts, Diether and Lazaro, Conxi and Leslie, Goska and Lester, Jenny and Lesueur, Fabienne and Lindstr{\"o}m, Sara and Long, Jirong and Loud, Jennifer T. and Lubiński, Jan and Makalic, Enes and Mannermaa, Arto and Manoochehri, Mehdi and Margolin, Sara and Maurer, Tabea and Mavroudis, Dimitrios and McGuffog, Lesley and Meindl, Alfons and Menon, Usha and Michailidou, Kyriaki and Miller, Austin and Montagna, Marco and Moreno, Fernando and Moserle, Lidia and Mulligan, Anna Marie and Nathanson, Katherine L. and Neuhausen, Susan L. and Nevanlinna, Heli and Nevelsteen, Ines and Nielsen, Finn C. and Nikitina-Zake, Liene and Nussbaum, Robert L. and Offit, Kenneth and Olah, Edith and Olopade, Olufunmilayo I. and Olsson, H{\aa}kan and Osorio, Ana and Papp, Janos and Park-Simon, Tjoung-Won and Parsons, Michael T. and Pedersen, Inge Sokilde and Peixoto, Ana and Peterlongo, Paolo and Pharaoh, Paul D. P. and Plaseska-Karanfilska, Dijana and Poppe, Bruce and Presneau, Nadege and Radice, Paolo and Rantala, Johanna and Rennert, Gad and Risch, Harvey A. and Saloustros, Emmanouil and Sanden, Kristin and Sawyer, Elinor J. and Schmidt, Marjanka K. and Schmutzler, Rita K. and Sharma, Priyanka and Shu, Xiao-Ou and Simard, Jaques and Singer, Christian F. and Soucy, Penny and Southey, Melissa C. and Spinelli, John J. and Spurdle, Amanda B. and Stone, Jennifer and Swerdlow, Anthony J. and Tapper, William J. and Taylor, Jack A. and Teixeira, Manuel R. and Terry, Mary Beth and Teul{\´e}, Alex and Thomassen, Mads and Th{\"o}ne, Kathrin and Thull, Darcy L. and Tischkowitz, Marc and Toland, Amanda E. and Torres, Diana and Truong, Th{\´e}r{\`e}se and Tung, Nadine and Vachon, Celine M. and van Asperen, Christi J. and van den Ouweland, Ans M. W. and van Rensburg, Elizabeth J. and Vega, Ana and Viel, Alexandra and Wang, Qin and Wappenschmidt, Barbara and Weitzel, Jeffrey N. and Wendt, Camilla and Winqvist, Robert and Yang, Xiaohong R. and Yannoukakos, Drakoulis and Ziogas, Argyrios and Kraft, Peter and Antoniou, Antonis C. and Zheng, Wei and Easton, Douglas F. and Milne, Roger L. and Beesley, Jonathan and Chenevix-Trench, Georgia}, title = {Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, organization = {EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators}, doi = {10.1038/s41467-018-08053-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228024}, year = {2019}, abstract = {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.}, language = {en} } @article{RoelofsBlackburnLindahletal.2023, author = {Roelofs, Freek and Blackburn, Lindy and Lindahl, Greg and Doeleman, Sheperd S. and Johnson, Michael D. and Arras, Philipp and Chatterjee, Koushik and Emami, Razieh and Fromm, Christian and Fuentes, Antonio and Knollm{\"u}ller, Jakob and Kosogorov, Nikita and M{\"u}ller, Hendrik and Patel, Nimesh and Raymond, Alexander and Tiede, Paul and Traianou, Efthalia and Vega, Justin}, title = {The ngEHT analysis challenges}, series = {Galaxies}, volume = {11}, journal = {Galaxies}, number = {1}, issn = {2075-4434}, doi = {10.3390/galaxies11010012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304976}, year = {2023}, abstract = {The next-generation Event Horizon Telescope (ngEHT) will be a significant enhancement of the Event Horizon Telescope (EHT) array, with ∼10 new antennas and instrumental upgrades of existing antennas. The increased uv-coverage, sensitivity, and frequency coverage allow a wide range of new science opportunities to be explored. The ngEHT Analysis Challenges have been launched to inform the development of the ngEHT array design, science objectives, and analysis pathways. For each challenge, synthetic EHT and ngEHT datasets are generated from theoretical source models and released to the challenge participants, who analyze the datasets using image reconstruction and other methods. The submitted analysis results are evaluated with quantitative metrics. In this work, we report on the first two ngEHT Analysis Challenges. These have focused on static and dynamical models of M87* and Sgr A* and shown that high-quality movies of the extended jet structure of M87* and near-horizon hourly timescale variability of Sgr A* can be reconstructed by the reference ngEHT array in realistic observing conditions using current analysis algorithms. We identify areas where there is still room for improvement of these algorithms and analysis strategies. Other science cases and arrays will be explored in future challenges.}, language = {en} } @article{JohnsonAkiyamaBlackburnetal.2023, author = {Johnson, Michael D. and Akiyama, Kazunori and Blackburn, Lindy and Bouman, Katherine L. and Broderick, Avery E. and Cardoso, Vitor and Fender, Rob P. and Fromm, Christian M. and Galison, Peter and G{\´o}mez, Jos{\´e} L. and Haggard, Daryl and Lister, Matthew L. and Lobanov, Andrei P. and Markoff, Sera and Narayan, Ramesh and Natarajan, Priyamvada and Nichols, Tiffany and Pesce, Dominic W. and Younsi, Ziri and Chael, Andrew and Chatterjee, Koushik and Chaves, Ryan and Doboszewski, Juliusz and Dodson, Richard and Doeleman, Sheperd S. and Elder, Jamee and Fitzpatrick, Garret and Haworth, Kari and Houston, Janice and Issaoun, Sara and Kovalev, Yuri Y. and Levis, Aviad and Lico, Rocco and Marcoci, Alexandru and Martens, Niels C. M. and Nagar, Neil M. and Oppenheimer, Aaron and Palumbo, Daniel C. M. and Ricarte, Angelo and Rioja, Mar{\´i}a  J. and Roelofs, Freek and Thresher, Ann C. and Tiede, Paul and Weintroub, Jonathan and Wielgus, Maciek}, title = {Key science goals for the next-generation Event Horizon Telescope}, series = {Galaxies}, volume = {11}, journal = {Galaxies}, number = {3}, issn = {2075-4434}, doi = {10.3390/galaxies11030061}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313525}, year = {2023}, abstract = {The Event Horizon Telescope (EHT) has led to the first images of a supermassive black hole, revealing the central compact objects in the elliptical galaxy M87 and the Milky Way. Proposed upgrades to this array through the next-generation EHT (ngEHT) program would sharply improve the angular resolution, dynamic range, and temporal coverage of the existing EHT observations. These improvements will uniquely enable a wealth of transformative new discoveries related to black hole science, extending from event-horizon-scale studies of strong gravity to studies of explosive transients to the cosmological growth and influence of supermassive black holes. Here, we present the key science goals for the ngEHT and their associated instrument requirements, both of which have been formulated through a multi-year international effort involving hundreds of scientists worldwide.}, language = {en} } @article{ChatterjeeChaelTiedeetal.2023, author = {Chatterjee, Koushik and Chael, Andrew and Tiede, Paul and Mizuno, Yosuke and Emami, Razieh and Fromm, Christian and Ricarte, Angelo and Blackburn, Lindy and Roelofs, Freek and Johnson, Michael D. and Doeleman, Sheperd S. and Arras, Philipp and Fuentes, Antonio and Knollm{\"u}ller, Jakob and Kosogorov, Nikita and Lindahl, Greg and M{\"u}ller, Hendrik and Patel, Nimesh and Raymond, Alexander and Traianou, Efthalia and Vega, Justin}, title = {Accretion flow morphology in numerical simulations of black holes from the ngEHT model library: the impact of radiation physics}, series = {Galaxies}, volume = {11}, journal = {Galaxies}, number = {2}, issn = {2075-4434}, doi = {10.3390/galaxies11020038}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304084}, year = {2023}, abstract = {In the past few years, the Event Horizon Telescope (EHT) has provided the first-ever event horizon-scale images of the supermassive black holes (BHs) M87* and Sagittarius A* (Sgr A*). The next-generation EHT project is an extension of the EHT array that promises larger angular resolution and higher sensitivity to the dim, extended flux around the central ring-like structure, possibly connecting the accretion flow and the jet. The ngEHT Analysis Challenges aim to understand the science extractability from synthetic images and movies to inform the ngEHT array design and analysis algorithm development. In this work, we compare the accretion flow structure and dynamics in numerical fluid simulations that specifically target M87* and Sgr A*, and were used to construct the source models in the challenge set. We consider (1) a steady-state axisymmetric radiatively inefficient accretion flow model with a time-dependent shearing hotspot, (2) two time-dependent single fluid general relativistic magnetohydrodynamic (GRMHD) simulations from the H-AMR code, (3) a two-temperature GRMHD simulation from the BHAC code, and (4) a two-temperature radiative GRMHD simulation from the KORAL code. We find that the different models exhibit remarkably similar temporal and spatial properties, except for the electron temperature, since radiative losses substantially cool down electrons near the BH and the jet sheath, signaling the importance of radiative cooling even for slowly accreting BHs such as M87*. We restrict ourselves to standard torus accretion flows, and leave larger explorations of alternate accretion models to future work.}, language = {en} }