title: Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.
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)].
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Litchfield
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Razvan
authors.initials: R
authors.lastname: Sultana
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Renwick
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Darshna
authors.initials: D
authors.lastname: Dudakia
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Ramsay
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Silvana
authors.initials: S
authors.lastname: Powell
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Elliott
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Warren-Perry
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK, Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.affiliation: Non-communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.affiliation: Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, UK.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Nsengimana
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.affiliation: Genetic Epidemiology Unit, Strangeways Research Laboratory, Cancer Research UK, Cambridge, UK and.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds, UK.
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.affiliation: Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Huddart
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK, Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK, Royal Marsden NHS Foundation Trust, London, UK, clare.turnbull@icr.ac.uk.
authors.forename: Clare
authors.initials: C
authors.lastname: Turnbull
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013736:Testicular Neoplasms