Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Florez, J.C. et al.

J.C. Florez, M. Sjögren, C.M. Agapakis, N.P. Burtt, P. Almgren, U. Lindblad, G. Berglund, T. Tuomi, D. Gaudet, M.J. Daly, K.G. Ardlie, J.N. Hirschhorn, D. Altshuler, L. Groop,

Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes.

AIMS/HYPOTHESIS: Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants might account for the putative association signal. SUBJECTS AND METHODS: We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers in several family-based and case-control samples of European descent totalling 12,129 subjects. RESULTS: In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p = 0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96-1.39, p = 0.059). The combined OR was 1.20 (p = 0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits. CONCLUSIONS/INTERPRETATION: Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.[1]

References

Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes. Florez, J.C., Sjögren, M., Agapakis, C.M., Burtt, N.P., Almgren, P., Lindblad, U., Berglund, G., Tuomi, T., Gaudet, D., Daly, M.J., Ardlie, K.G., Hirschhorn, J.N., Altshuler, D., Groop, L. Diabetologia (2007) [Pubmed]

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