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Association testing...
Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes
- Article/chapterEnglish2004
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American Diabetes Association,2004
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LIBRIS-ID:oai:lup.lub.lu.se:9239dd3e-cdba-4b56-82df-97416871583d
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https://lup.lub.lu.se/record/259896URI
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https://doi.org/10.2337/diabetes.53.12.3313DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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The insulin receptor substrate (IRS)-1 is an important component of the insulin signal transduction cascade. Several reports suggest that a Gly-->Arg change in codon 972 is associated with type 2 diabetes and related traits, and a recent meta-analysis reported a modest but nominally significant association with type 2 diabetes (odds ratio [OR] 1.25 in favor of carriers of the Arg allele [95% CI 1.05-1.48). To test the reproducibility of the model in a recent meta-analysis, we examined genotype-phenotype correlation in three large Caucasian samples (not previously reported for this variant) totaling 9,000 individuals (estimated to have >95% power to obtain a P<0.05 for the OR of 1.25 estimated in the meta-analysis). In our combined sample, comprising 4,279 case and 3,532 control subjects, as well as 1,189 siblings discordant for type 2 diabetes, G972R was not associated with type 2 diabetes (OR 0.96 [0.84-1.10], P = 0.60). Genotype at G972R had no significant effect on various measures of insulin secretion or insulin resistance in a set of Scandinavian samples in whom we had detailed phenotypic data. In contrast, the well-documented associations of peroxisome proliferator-activated receptor gamma P12A and Kir6.2 E23K with type 2 diabetes are both robustly observed in these 9,000 subjects, including an additional (previously unpublished) confirmation of Kir6.2 E23K and type 2 diabetes in the Polish and North American samples (combined OR 1.15 [1.05-1.261, P = 0.001). Despite genotyping 9,000 people and >95% power to reproduce the estimated OR from the recent meta-analysis, we were unable to replicate the association of the IRS-1 G972R polymorphism with type 2 diabetes.
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Sjögren, MarketaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-msj
(author)
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Burtt, N
(author)
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Orho-Melander, MarjuLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-mor
(author)
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Schayer, S
(author)
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Sun, M
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Almgren, PeterLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-pal
(author)
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Lindblad, UlfLund University,Lunds universitet,Samhällsmedicin,Forskargrupper vid Lunds universitet,Community Medicine,Lund University Research Groups(Swepub:lu)smi-uli
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Tuomi, T
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Gaudet, D
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Hudson, TJ
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Daly, MJ
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Ardlie, KG
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Hirschhorn, JN
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Altshuler, D
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Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr
(author)
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Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet
(creator_code:org_t)
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In:Diabetes: American Diabetes Association53:12, s. 3313-33181939-327X0012-1797
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Diabetes
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Florez, JC
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Sjögren, Marketa
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Burtt, N
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Orho-Melander, M ...
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Schayer, S
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Sun, M
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Almgren, Peter
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Lindblad, Ulf
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Tuomi, T
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Gaudet, D
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Hudson, TJ
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Daly, MJ
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Ardlie, KG
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Hirschhorn, JN
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Altshuler, D
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Groop, Leif
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