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Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

ABSTRACT: Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.

SUBMITTER: Salonen JT

PROVIDER: S-EPMC1950819 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

Salonen Jukka T JT Uimari Pekka P Aalto Juha-Matti JM Pirskanen Mia M Kaikkonen Jari J Todorova Boryana B Hyppönen Jelena J Korhonen Veli-Pekka VP Asikainen Janne J Devine Christopher C Tuomainen Tomi-Pekka TP Luedemann Jan J Nauck Matthias M Kerner Wolfgang W Stephens Richard H RH New John P JP Ollier William E WE Gibson J Martin JM Payton Antony A Horan Michael A MA Pendleton Neil N Mahoney Walt W Meyre David D Delplanque Jerôme J Froguel Philippe P Luzzatto Oren O Yakir Benjamin B Darvasi Ariel A

American journal of human genetics 20070626 2

Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. ...[more]

PMID: 17668382

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Project description:Cases with Type 1 Diabetes (T1D) in the UK, were part of the Wellcome Trust Case Control Consortium (WTCCC) - <a href="http://www.wtccc.org.uk" target="_blank">http://www.wtccc.org.uk</a> - that first reported in 2007: Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661-678. [PubMed: <a href="http://www.ncbi.nlm.nih.gov/pubmed/17554300" target="_blank">17554300</a>] In this genome-wide association study (GWAS), funded by the NIH and JDRF, and sponsored by the Type 1 Diabetes Genetics Consortium (T1DGC), we were able to extend the case and control groups used in the WTCCC, with the intention of performing a well-powered meta-analysis. The study is written up as: Barrett, J.C., Clayton, D.G., Concannon, P., Akolkar, B., Cooper, J.D., Erlich, H.A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Plagnol, V., Pociot, F., Schuilenburg, H., Smyth, D.J., Stevens, H., Todd, J.A., Walker, N.M., Rich, S.S. and The Type 1 Diabetes Genetics Consortium Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19430480" target="_blank">19430480</a>. Resources - data: * Case data from this study is deposited here (i.e. in dbGaP) * Control data from this experiment - with subjects from the 1958 British Birth Cohort - is deposited with the European Genotype Archive (EGA): <a href="http://www.ebi.ac.uk/ega/" target="_blank">http://www.ebi.ac.uk/ega/</a> from where the WTCCC data is also available. * A complete description of how to request all components of the meta-analysis is available at: <a href="http://www.t1dbase.org/page/PosterView/display/poster_id/324" target="_blank">http://www.t1dbase.org/page/PosterView/display/poster_id/324</a> * Additional genetic data on the same case subjects, including some HLA types, are available from the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory (JDRF/WT-DIL): <a href="http://www-gene.cimr.cam.ac.uk/todd/" target="_blank">http://www-gene.cimr.cam.ac.uk/todd/</a> Resources - samples: Case and control DNA samples are also available: * Case DNA samples are available from the JDRF/WT-DIL, as above, and will be available from the NIDDK Genetics Repository at Rutgers: <a href="https://www.niddkrepository.org" target="_blank">https://www.niddkrepository.org</a> * Control DNA samples are available from the 1958 British Birth Cohort (aka National Child Development Study): <a href="http://www.cls.ioe.ac.uk/studies.asp?section=000100020003" target="_blank">http://www.cls.ioe.ac.uk/studies.asp?section=000100020003</a> Use restrictions: There are access limitations to both data and samples, in order to keep their use in line with subjects' consent.

Dataset Information

Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

Publications

Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

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