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Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor.

Title: Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor.
Authors: 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
Contributors: Litchfield, Kevin; Turnbull, Clare
Publisher Information: NATURE PORTFOLIO
Publication Year: 2020
Collection: The Institute of Cancer Research (ICR): Publications Repository
Subject Terms: Testicular Cancer Consortium; Chromosomes; Human; 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
Description: 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.
Document Type: article in journal/newspaper
File Description: Print-Electronic; 1147; application/pdf
Language: English
ISSN: 1546-1718; 1061-4036
Relation: Nature genetics, 2017, 49 (7), pp. 1141 - 1147; https://repository.icr.ac.uk/handle/internal/4006
DOI: 10.1038/ng.3879
Availability: https://doi.org/10.1038/ng.3879; https://repository.icr.ac.uk/handle/internal/4006
Rights: https://www.rioxx.net/licenses/all-rights-reserved
Accession Number: edsbas.2E1915E0
Database: BASE