Sex specific associations in genome wide association analysis of renal cell carcinoma

Ruhina S. Laskar, David C. Muller, Peng Li, Mitchell J. Machiela, Yuanqing Ye, Valerie Gaborieau, Matthieu Foll, Jonathan N. Hofmann, Leandro Colli, Joshua N. Sampson, Zhaoming Wang, Delphine Bacq-Daian, Anne Boland, Behnoush Abedi-Ardekani, Geoffroy Durand, Florence Le Calvez-Kelm, Nivonirina Robinot, Helene Blanche, Egor Prokhortchouk, Konstantin G. SkryabinLaurie Burdett, Meredith Yeager, Sanja Radojevic-Skodric, Slavisa Savic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Stefan Rascu, Anush Mukeria, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Beata Świątkowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, Antonia Trichopoulou, Elio Riboli, Kim Overvad, Salvatore Panico, Borje Ljungberg, Raviprakash T. Sitaram, Graham G. Giles, Roger L. Milne, Gianluca Severi, Fiona Bruinsma, Tony Fletcher, Kvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Männistö, Stephanie Weinstein, Peter E. Clark, Todd L. Edwards, Loren Lipworth, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard D. Sesso, Amanda Black, Neal D. Freedman, Wen Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Bin Tean Teh, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Wong Ho Chow, Lee E. Moore, Toni K. Choueiri, Christopher Wood, Mattias Johansson, James D. McKay, Kevin M. Brown, Nathaniel Rothman, Mark G. Lathrop, Jean Francois Deleuze, Xifeng Wu, Paul Brennan, Stephen J. Chanock, Mark P. Purdue, Ghislaine Scelo

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27 Citations (Scopus)

Abstract

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10−8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90–1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10−8 compared with ORfemale = 0.93 [95% CI = 0.82–1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

Original languageEnglish
Pages (from-to)1589-1598
Number of pages10
JournalEuropean Journal of Human Genetics
Volume27
Issue number10
DOIs
Publication statusPublished - 1 Oct 2019
Externally publishedYes

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