A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk
Authors: Yingchang Lu, Alicia Beeghly-Fadiel, Lang Wu, Xingyi Guo, Bingshan Li, Joellen M. Schildkraut, Hae Kyung Im, Yian A. Chen, Jennifer B. Permuth, Brett M. Reid, Jamie K. Teer, Kirsten B. Moysich, Irene L. Andrulis, Hoda Anton-Culver, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Javier Benitez, Line Bjorge, James Brenton, Ralf Butzow, Trinidad Caldes, Maria A. Caligo, Ian Campbell, Jenny Chang-Claude, Kathleen B.M. Claes, Fergus J. Couch, Daniel W. Cramer, Mary B. Daly, Anna deFazio, Joe Dennis, Orland Diez, Susan M. Domchek, Thilo Dörk, Douglas F. Easton, Diana M. Eccles, Peter A. Fasching, Renée T. Fortner, George Fountzilas, Eitan Friedman, Patricia A. Ganz, Judy Garber, Graham G. Giles, Andrew K. Godwin, David E. Goldgar, Marc T. Goodman, Mark H. Greene, Jacek Gronwald, Ute Hamann, Florian Heitz, Michelle A.T. Hildebrandt, Claus K. Høgdall, Antoinette Hollestelle, Peter J. Hulick, David G. Huntsman, Evgeny N. Imyanitov, Claudine Isaacs, Anna Jakubowska, Paul James, Beth Y. Karlan, Linda E. Kelemen, Lambertus A. Kiemeney, Susanne K. Kjaer, Ava Kwong, Nhu D. Le, Goska Leslie, Fabienne Lesueur, Douglas A. Levine, Amalia Mattiello, Taymaa May, Lesley McGuffog, Iain A. McNeish, Melissa A. Merritt, Francesmary Modugno, Marco Montagna, Susan L. Neuhausen, Heli Nevanlinna, Finn C. Nielsen, Liene Nikitina-Zake, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Sara H. Olson, Håkan Olsson, Ana Osorio, Sue K. Park, Michael T. Parsons, Petra H.M. Peeters, Tanja Pejovic, Paolo Peterlongo, Catherine M. Phelan, Miquel Angel Pujana, Susan J. Ramus, Gad Rennert, Harvey Risch, Gustavo C. Rodriguez, Cristina Rodríguez-Antona, Isabelle Romieu, Matti A. Rookus, Mary Anne Rossing, Iwona K. Rzepecka, Dale P. Sandler, Rita K. Schmutzler, Veronica W. Setiawan, Priyanka Sharma, Weiva Sieh, Jacques Simard, Christian F. Singer, Honglin Song, Melissa C. Southey, Amanda B. Spurdle, Rebecca Sutphen, Anthony J. Swerdlow, Manuel R. Teixeira, Soo H. Teo, Mads Thomassen, Marc Tischkowitz, Amanda E. Toland, Antonia Trichopoulou, Nadine Tung, Shelley S. Tworoger, Elizabeth J. van Rensburg, Adriaan Vanderstichele, Ana Vega, Digna Velez Edwards, Penelope M. Webb, Jeffrey N. Weitzel, Nicolas Wentzensen, Emily White, Alicja Wolk, Anna H. Wu, Drakoulis Yannoukakos, Kristin K. Zorn, Simon A. Gayther, Antonis C. Antoniou, Andrew Berchuck, Ellen L. Goode, Georgia Chenevix-Trench, Thomas A. Sellers, Paul D.P. Pharoah, Wei Zheng, Jirong Long
Journal: Cancer Research (2018)

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their