TY - JOUR
T1 - Meta- A nalysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor
AU - Testicular Cancer Consortium
AU - Wang, Zhaoming
AU - McGlynn, Katherine A.
AU - Rajpert-De Meyts, Ewa
AU - Bishop, D. Timothy
AU - Chung, Charles C.
AU - Dalgaard, Marlene D.
AU - Greene, Mark H.
AU - Gupta, Ramneek
AU - Grotmol, Tom
AU - Haugen, Trine B.
AU - Karlsson, Robert
AU - Litchfield, Kevin
AU - Mitra, Nandita
AU - Nielsen, Kasper
AU - Pyle, Louise C.
AU - Schwartz, Stephen M.
AU - Thorsson, Vésteinn
AU - Vardhanabhuti, Saran
AU - Wiklund, Fredrik
AU - Turnbull, Clare
AU - Chanock, Stephen J.
AU - Kanetsky, Peter A.
AU - Nathanson, Katherine L.
AU - Ferlin, Alberto
AU - Gietema, Jourik A.
AU - Cortessis, Victoria
AU - Hauser, Russ
AU - Hildebrandt, Michelle
AU - Kiemeney, Lambertus A.
AU - Kubisch, Christian
AU - Lessel, Davor
AU - Rafnar, Thorunn
AU - Richiardi, Lorenzo
AU - Skotheim, Rolf
AU - Zheng, Tongzhang
N1 - Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta- A nalysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 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 familial 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 to the etiology of TGCT.
AB - The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta- A nalysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 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 familial 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 to the etiology of TGCT.
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U2 - 10.1038/ng.3879
DO - 10.1038/ng.3879
M3 - Article
C2 - 28604732
AN - SCOPUS:85021774725
SN - 1061-4036
VL - 49
SP - 1141
EP - 1146
JO - Nature Genetics
JF - Nature Genetics
IS - 7
ER -