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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
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Florez, JC (author)
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- Sjögren, Marketa (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Burtt, N (author)
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- Orho-Melander, Marju (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Schayer, S (author)
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Sun, M (author)
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- Almgren, Peter (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Lindblad, Ulf (author)
- Lund University,Lunds universitet,Samhällsmedicin,Forskargrupper vid Lunds universitet,Community Medicine,Lund University Research Groups
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Tuomi, T (author)
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Gaudet, D (author)
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Hudson, TJ (author)
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Daly, MJ (author)
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Ardlie, KG (author)
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Hirschhorn, JN (author)
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Altshuler, D (author)
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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(creator_code:org_t)
- American Diabetes Association, 2004
- 2004
- English.
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 53:12, s. 3313-3318
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Diabetes
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- By the author/editor
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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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show more...
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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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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Diabetes
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Lund University