@article{3181463,
    title = "A Transcriptome-Wide Association Study Among 97,898 Women to Identify
Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk",
    author = "Lu, Yingchang and Beeghly-Fadiel, Alicia and Wu, Lang and Guo, Xingyi and and Li, Bingshan and Schildkraut, Joellen M. and Im, Hae Kyung and Chen, and Yian A. and Permuth, Jennifer B. and Reid, Brett M. and Teer, Jamie K. and and Moysich, Kirsten B. and Andrulis, Irene L. and Anton-Culver, Hoda and and Arun, Banu K. and Bandera, Elisa V. and Barkardottir, Rosa B. and and Barnes, Daniel R. and Benitez, Javier and Bjorge, Line and Brenton, and James and Butzow, Ralf and Caldes, Trinidad and Caligo, Maria A. and and Campbell, Ian and Chang-Claude, Jenny and Claes, Kathleen B. M. and and Couch, Fergus J. and Cramer, DanielW. and Daly, Mary B. and deFazio, and Anna and Dennis, Joe and Diez, Orland and Domchek, Susan M. and Doerk, and Thilo and Easton, Douglas F. and Eccles, Diana M. and Fasching, Peter A. and and Fortner, Renee T. and Fountzilas, George and Friedman, Eitan and and Ganz, Patricia A. and Garber, Judy and Giles, Graham G. and Godwin, and Andrew K. and Goldgar, David E. and Goodman, Marc T. and Greene, Mark H. and and Gronwald, Jacek and Hamann, Ute and Heitz, Florian and Hildebrandt, and Michelle A. T. and Hogdall, Claus K. and Hollestelle, Antoinette and and Hulick, Peter J. and Huntsman, David G. and Imyanitov, Evgeny N. and and Isaacs, Claudine and Jakubowska, Anna and James, Paul and Karlan, Beth and Y. and Kelemen, Linda E. and Kiemeney, Lambertus A. and Kjaer, Susanne and K. and Kwong, Ava and Le, Nhu D. and Leslie, Goska and Lesueur, Fabienne and and Levine, Douglas A. and Mattiello, Amalia and May, Taymaa and and McGuffog, Lesley and McNeish, Iain A. and Merritt, Melissa A. and and Modugno, Francesmary and Montagna, Marco and Neuhausen, Susan L. and and Nevanlinna, Heli and Nielsen, Finn C. and Nikitina-Zake, Liene and and Nussbaum, Robert L. and Offit, Kenneth and Olah, Edith and Olopade, and Olufunmilayo I. and Olson, Sara H. and Olsson, Hakan and Osorio, Ana and and Park, Sue K. and Parsons, Michael T. and Peeters, Petra H. M. and and Pejovic, Tanja and Peterlongo, Paolo and Phelan, Catherine M. and and Pujana, Miquel Angel and Ramus, Susan J. and Rennert, Gad and Risch, and Harvey and Rodriguez, Gustavo C. and Rodriguez-Antona, Cristina and and Romieu, Isabelle and Rookus, Matti A. and Rossing, Mary Anne and and Rzepecka, Iwona K. and Sandler, Dale P. and Schmutzler, Rita K. and and Setiawan, Veronica W. and Sharma, Priyanka and Sieh, Weiva and Simard, and Jacques and Singer, Christian F. and Song, Honglin and Southey, Melissa and C. and Spurdle, Amanda B. and Sutphen, Rebecca and Swerdlow, Anthony J. and and Teixeira, Manuel R. and Teo, Soo H. and Thomassen, Mads and and Tischkowitz, Marc and Toland, Amanda E. and Trichopoulou, Antonia and and Tung, Nadine and Tworoger, Shelley S. and van Rensburg, Elizabeth J. and and Vanderstichele, Adriaan and Vega, Ana and Edwards, Digna Velez and Webb, and Penelope M. and Weitzel, Jeffrey N. and Wentzensen, Nicolas and White, and Emily and Wolk, Alicja and Wu, Anna H. and Yannoukakos, Drakoulis and and Zorn, Kristin K. and Gayther, Simon A. and Antoniou, Antonis C. and and Berchuck, Andrew and Goode, Ellen L. and Chenevix-Trench, Georgia and and Sellers, Thomas A. and Pharoah, Paul D. P. and Zheng, Wei and Long, and Jirong",
    journal = "Current Cancer Research",
    year = "2018",
    volume = "78",
    number = "18",
    pages = "5419-5430",
    publisher = "AMER ASSOC CANCER RESEARCH",
    doi = "10.1158/0008-5472.CAN-18-0951",
    abstract = "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 cis-predicted gene expression in relation to EOC risk
using summary statistics data from GWAS of 97,898 women, including
29,396 EOC cases. With a Bonferroni-corrected significance level of P <
2.2 x 10(-6), we identified 35 genes, including FZD4 at 11q14.2 (Z =
5.08, P = 3.83 x 10(-7), the cross-tissue model; 1 Mb away from any
GWAS-identified EOC risk variant), a potential novel locus for EOC risk.
All other 34 significantly associated genes were located within 1 Mb of
known GWAS-identified loci, including 23 genes at 6 loci not previously
linked to EOC risk. Upon conditioning on nearby known EOC
GWAS-identified variants, the associations for 31 genes disappeared and
three genes remained (P < 1.47 x 10(-3)). These data identify one novel
locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC
risk, providing new insights into EOC carcinogenesis.
Significance: Transcriptomic analysis of a large cohort confirms earlier
GWAS loci and reveals FZD4 as a novel locus associated with EOC risk.
(C) 2018 AACR."
}