Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor
Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa; Bishop, D. Timothy; Chung, Charles C.; Dalgaard, Marlene D.; Greene, Mark H.; Gupta, Ramneek; Grotmol, Tom; Haugen, Trine B.; Karlsson, Robert; Litchfield, Kevin; Mitra, Nandita; Nielsen, Kasper; Pyle, Louise C.; Schwartz, Stephen M.; Thorsson, Vesteinn; Vardhanabhuti, Saran; Wiklund, Fredrik; Turnbull, Clare; Chanock, Stephen J.; Kanetsky, Peter A.; Nathanson, Katherine L.
Journal article, Peer reviewed
MetadataShow full item record
Original versionWang Z, McGlynn KA, Rajpert-De Meyts E, Bishop DT, Chung CC, Dalgaard, Greene MH, Gupta R, Grotmol T, Haugen TB, Karlsson R, Litchfield K, Mitra N, Nielsen, Pyle, Schwartz SM, Thorsson, Vardhanabhuti S, Wiklund F, Turnbull C, Chanock SJ, Kanetsky PA, Nathanson KL. Meta- A nalysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor. Nature Genetics. 2017;49(7):1141-1147 http://dx.doi.org/10.1038/ng.3879
The international TEsticular CAncer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumors (TGCT; 3,558 cases and 13,970 controls) to identify novel susceptibility loci. We conducted a fixed effects meta-analysis, including the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 59 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5×10-8). Most loci harbor biologically plausible candidate genes. We refined previously reported associations at 9p24.3 and 19p12 by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT susceptibility alleles, move the field closer to a comprehensive understanding of the underlying genetic architecture of TGCT, and provide further clues into the etiology of TGCT.