Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor
Standard
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, Vésteinn; Vardhanabhuti, Saran; Wiklund, Fredrik; Turnbull, Clare; Chanock, Stephen J; Kanetsky, Peter A; Nathanson, Katherine L; Testicular Cancer Consortium.
In: NAT GENET, Vol. 49, No. 7, 07.2017, p. 1141-1147.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor
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 - Testicular Cancer Consortium
PY - 2017/7
Y1 - 2017/7
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-analysis, 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-analysis, 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.
KW - Adult
KW - Chromosome Mapping
KW - Chromosomes, Human, X
KW - Computational Biology
KW - Computer Simulation
KW - Family Health
KW - Genetic Markers
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Haplotypes
KW - Humans
KW - Male
KW - Neoplasms, Germ Cell and Embryonal
KW - Polymorphism, Single Nucleotide
KW - Risk
KW - Testicular Neoplasms
KW - Young Adult
KW - Journal Article
KW - Meta-Analysis
U2 - 10.1038/ng.3879
DO - 10.1038/ng.3879
M3 - SCORING: Journal article
C2 - 28604732
VL - 49
SP - 1141
EP - 1147
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 7
ER -