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

Florez, J. C.; Sjögren, Marketa LU ; Agapakis, C. M.; Burtt, N. P.; Almgren, Peter LU ; Lindblad, Ulf LU ; Berglund, Göran LU ; Tuomi, T.; Gaudet, D. and Daly, M. J., et al. (2007) In Diabetologia 50(6). p.1209-1217
Abstract
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... (More)
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. Conclusion/interpretation Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent. (Less)
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Contribution to journal
publication status
published
subject
keywords
SNP, type 2 diabetes, common variants, insulin resistance, IRS1, disequilibrium, linkage, single nucleotide polymorphism, genetic association
in
Diabetologia
volume
50
issue
6
pages
1209 - 1217
publisher
Springer Verlag
external identifiers
  • wos:000246271600013
  • scopus:34247844402
ISSN
1432-0428
DOI
10.1007/s00125-007-0657-5
language
English
LU publication?
yes
id
bf907fe2-a745-4cd4-95c1-ac48da2b0833 (old id 660539)
date added to LUP
2007-12-10 13:06:50
date last changed
2017-03-05 03:40:06
@article{bf907fe2-a745-4cd4-95c1-ac48da2b0833,
  abstract     = {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. Conclusion/interpretation Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.},
  author       = {Florez, J. C. and Sjögren, Marketa and Agapakis, C. M. and Burtt, N. P. and Almgren, Peter and Lindblad, Ulf and Berglund, Göran and Tuomi, T. and Gaudet, D. and Daly, M. J. and Ardlie, K. G. and Hirschhorn, J. N. and Altshuler, D. and Groop, Leif},
  issn         = {1432-0428},
  keyword      = {SNP,type 2 diabetes,common variants,insulin resistance,IRS1,disequilibrium,linkage,single nucleotide polymorphism,genetic association},
  language     = {eng},
  number       = {6},
  pages        = {1209--1217},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-007-0657-5},
  volume       = {50},
  year         = {2007},
}