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


Litchfield, K; Sultana, R; Renwick, A; Dudakia, D; Seal, S; Ramsay, E; Powell, S; Elliott, A; Warren-Perry, M; Eeles, R; Peto, J; Kote-Jarai, Z; Muir, K; Nsengimana, J; UKTCC, ; Stratton, MR; Easton, DF; Bishop, DT; Huddart, RA; Rahman, N; Turnbull, C; UKTCC, ; , COLLABORATORS; Pugh, J; Linger, R; Marke, J; Hughes, D; Pernet, D; Hall, P; Easton, DF; Berchuck, A; Eeles, R; Chenevix-Trench, G; Dennis, J; Dunning, AM; Lee, A; Dicks, E; Easton, DF; Benitez, J; Gonzalez-Neira, A; Simard, J; Tessier, DC; Bacot, F; Vincent, D; LaBoissière, S; Robidoux, F; Bojesen, SE; Nielsen, SF; Nordestgaard, BG; Cunningham, JM; Windebank, SA; Hilker, CA; Meyer, J; (2014) Multi-stage genome wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25. Human molecular genetics, 24 (4). pp. 1169-76. ISSN 0964-6906 DOI: https://doi.org/10.1093/hmg/ddu511

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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)].<br/>

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Social and Environmental Health Research
Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 25281660
Web of Science ID: 350138300022
URI: http://researchonline.lshtm.ac.uk/id/eprint/2006407

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