Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor.
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Date
2017-07-01Author
Wang, Z
McGlynn, KA
Rajpert-De Meyts, E
Bishop, DT
Chung, CC
Dalgaard, MD
Greene, MH
Gupta, R
Grotmol, T
Haugen, TB
Karlsson, R
Litchfield, K
Mitra, N
Nielsen, K
Pyle, LC
Schwartz, SM
Thorsson, V
Vardhanabhuti, S
Wiklund, F
Turnbull, C
Chanock, SJ
Kanetsky, PA
Nathanson, KL
Testicular Cancer Consortium,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Testicular Cancer Consortium
Chromosomes, Human, X
Humans
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Genetic Predisposition to Disease
Genetic Markers
Risk
Chromosome Mapping
Computational Biology
Genotype
Haplotypes
Polymorphism, Single Nucleotide
Computer Simulation
Adult
Family Health
Male
Genome-Wide Association Study
Young Adult
Research team
Molecular & Population Genetics
Language
eng
Date accepted
2017-04-27
License start date
2017-07
Citation
Nature genetics, 2017, 49 (7), pp. 1141 - 1147
Publisher
NATURE PORTFOLIO