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PMID: 12739029 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study.

Diabetologia ·Vol. 46 ·No. 4 ·2003-04-00 ·Pages 579-87

Panhuysen CI, Cupples LA, Wilson PW, Herbert AG, Myers RH, Meigs JB

Abstract

Hyperinsulinaemia and insulin resistance usually precede clinical hyperglycaemia and Type 2 diabetes. Thus, plasma insulin concentrations and insulin resistance are important quantitative traits associated with risk of Type 2 diabetes, and represent key measures for genetic analysis of the syndrome. We carried out a genome-wide search for loci related to plasma insulin concentrations and insulin resistance in 330 extended, community-based pedigrees from the Framingham Heart Study. Normalized deviates of the standardized residuals of plasma insulin concentrations in the fasting state, 2 h after oral glucose challenge and as a measure of insulin resistance were used in linkage analysis with the variance components model implemented in the computer program SOLAR. The results suggest susceptibility loci influencing plasma concentrations of fasting insulin and insulin resistance on chromosomes 11 (LOD 2.43 at 85 cM close to D11S2002) and 17 (LOD 1.8 at 60 cM, close to D17S784); and susceptibility loci influencing 2-h plasma insulin concentrations on chromosomes 9 (LOD 2.8 at 80 cM, close to D9S922) and 19 (LOD 1.8 at 66 cM, close to D19S245). The results of the analysis of 1000 simulations of the trait and an unlinked marker suggest that in a genome scan of 401 markers fewer than one LOD score over 1 would be due to Type 1 error, and be a false positive. We conclude that these suggestive regions for quantitative pre-diabetic insulin traits could contain major loci in the pathogenesis of Type 2 diabetes.

MeSH Terms
Adolescent Adult Child Diabetes Mellitus, Type 2/genetics Female Genetic Predisposition to Disease/genetics Genetic Testing/methods Genome, Human Humans Insulin/blood,genetics Insulin Resistance Lod Score Male Middle Aged Quantitative Trait Loci/genetics
Chemicals
Insulin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Panhuysen C I M
Department of Biostatistics, Boston University School of Public Health and School of Medicine, Boston, MA, USA.
Cupples L A
Wilson P W F
Herbert A G
Myers R H
Meigs J B
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/s00125-003-1066-z
Published
2003-04-00
Epub
2003-00-21
Pages
579-87
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
Grants
NHLBI NIH HHS · N01-HC-38083 · United States
NHLBI NIH HHS · P01-HL41484 · United States
Corrections
CommentIn
PMID: 14576979
External Links
PubMed source DOI: 10.1007/s00125-003-1066-z View journal details
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