Dataset Information

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

ABSTRACT: Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)).

SUBMITTER: Eeles RA

PROVIDER: S-EPMC2846760 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

Eeles Rosalind A RA Kote-Jarai Zsofia Z Al Olama Ali Amin AA Giles Graham G GG Guy Michelle M Severi Gianluca G Muir Kenneth K Hopper John L JL Henderson Brian E BE Haiman Christopher A CA Schleutker Johanna J Hamdy Freddie C FC Neal David E DE Donovan Jenny L JL Stanford Janet L JL Ostrander Elaine A EA Ingles Sue A SA John Esther M EM Thibodeau Stephen N SN Schaid Daniel D Park Jong Y JY Spurdle Amanda A Clements Judith J Dickinson Joanne L JL Maier Christiane C Vogel Walther W Dörk Thilo T Rebbeck Timothy R TR Cooney Kathleen A KA Cannon-Albright Lisa L Chappuis Pierre O PO Hutter Pierre P Zeegers Maurice M Kaneva Radka R Zhang Hong-Wei HW Lu Yong-Jie YJ Foulkes William D WD English Dallas R DR Leongamornlert Daniel A DA Tymrakiewicz Malgorzata M Morrison Jonathan J Ardern-Jones Audrey T AT Hall Amanda L AL O'Brien Lynne T LT Wilkinson Rosemary A RA Saunders Edward J EJ Page Elizabeth C EC Sawyer Emma J EJ Edwards Stephen M SM Dearnaley David P DP Horwich Alan A Huddart Robert A RA Khoo Vincent S VS Parker Christopher C CC Van As Nicholas N Woodhouse Christopher J CJ Thompson Alan A Christmas Tim T Ogden Chris C Cooper Colin S CS Southey Melissa C MC Lophatananon Artitaya A Liu Jo-Fen JF Kolonel Laurence N LN Le Marchand Loic L Wahlfors Tiina T Tammela Teuvo L TL Auvinen Anssi A Lewis Sarah J SJ Cox Angela A FitzGerald Liesel M LM Koopmeiners Joseph S JS Karyadi Danielle M DM Kwon Erika M EM Stern Mariana C MC Corral Roman R Joshi Amit D AD Shahabi Ahva A McDonnell Shannon K SK Sellers Thomas A TA Pow-Sang Julio J Chambers Suzanne S Aitken Joanne J Gardiner R A Frank RA Batra Jyotsna J Kedda Mary Anne MA Lose Felicity F Polanowski Andrea A Patterson Briony B Serth Jürgen J Meyer Andreas A Luedeke Manuel M Stefflova Klara K Ray Anna M AM Lange Ethan M EM Farnham Jim J Khan Humera H Slavov Chavdar C Mitkova Atanaska A Cao Guangwen G Easton Douglas F DF

Nature genetics 20090920 10

Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving ...[more]

PMID: 19767753

Similar Datasets

Project description:BackgroundOsteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity.MethodsWe undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent.FindingsWe identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects.InterpretationOur findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.FundingarcOGEN was funded by a special purpose grant from Arthritis Research UK.

Dataset Information

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

Publications

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets