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Hum Mol Genet. 2015 Feb 15;24(4):1169-76. doi: 10.1093/hmg/ddu511. Epub 2014 Oct 3.

Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.

Author information

1
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
2
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK, Royal Marsden NHS Foundation Trust, London, UK.
3
Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
4
Institute of Population Health, University of Manchester, Manchester, UK.
5
Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, UK.
6
The Wellcome Trust Sanger Institute, Hinxton, UK.
7
Genetic Epidemiology Unit, Strangeways Research Laboratory, Cancer Research UK, Cambridge, UK and.
8
Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
9
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK, Royal Marsden NHS Foundation Trust, London, UK, clare.turnbull@icr.ac.uk.

Abstract

Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10(-9)].

PMID:
25281660
PMCID:
PMC4375409
DOI:
10.1093/hmg/ddu511
[Indexed for MEDLINE]
Free PMC Article

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