Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction.

Hdl Handle:
http://hdl.handle.net/10675.2/42
Title:
Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction.
Authors:
Wang, X; Ding, Xiuhua; Su, S; Spector, T D; Mangino, M; Iliadou, Anastasia; Snieder, H
Abstract:
AIMS/HYPOTHESIS: Evidence from candidate gene studies suggests that obesity may modify genetic susceptibility to type 2 diabetes and dyslipidaemia. On an aggregate level, gene-obesity interactions are expected to result in different heritability estimates at different obesity levels. However, this hypothesis has never been tested. METHOD: The present study included 2,180 British female twins. BMI was used as an index of general obesity. Outcome measures were insulin sensitivity (indexed by quantitative insulin-sensitivity check index [QUICKI]) and fasting plasma lipid profile. Structural equation modelling was used to test whether BMI interacted with latent genetic and environmental effects to impact on the outcome measures. RESULTS: Genetic influences on triacylglycerol increased with BMI (p < 0.001) whereas the unique environmental influence on QUICKI decreased with BMI (p < 0.001), resulting in a higher heritability estimate for both measures at higher BMI levels. This was further illustrated by stratified analysis in twin pairs concordant for normal weight and twin pairs concordant for overweight. Heritability was 19 percentage points higher for triacylglycerol (p < 0.001) and 31 percentage points higher for QUICKI (p < 0.01) among twins concordant for overweight than among twins concordant for normal weight. BMI had no moderator effect on the latent genetic and environmental factors for total cholesterol and HDL-cholesterol. CONCLUSIONS/INTERPRETATION: Our results suggest that the expression of genes influencing triacylglycerol and insulin sensitivity can vary as a function of obesity status. The substantial increases in the genetic contribution to the total variance in insulin sensitivity and triacylglycerols at higher BMIs may prove extremely valuable in the search for candidate genes.
Citation:
Diabetologia. 2009 Dec 11; 52(12):2578-2584
Issue Date:
21-Jan-2010
URI:
http://hdl.handle.net/10675.2/42
DOI:
10.1007/s00125-009-1524-3
PubMed ID:
19820914
PubMed Central ID:
PMC2776165
Type:
Journal Article; Twin Study
ISSN:
1432-0428
Appears in Collections:
Georgia Prevention Center: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Xen_US
dc.contributor.authorDing, Xiuhuaen_US
dc.contributor.authorSu, Sen_US
dc.contributor.authorSpector, T Den_US
dc.contributor.authorMangino, Men_US
dc.contributor.authorIliadou, Anastasiaen_US
dc.contributor.authorSnieder, Hen_US
dc.date.accessioned2010-09-24T21:20:21Z-
dc.date.available2010-09-24T21:20:21Z-
dc.date.issued2010-01-21en_US
dc.identifier.citationDiabetologia. 2009 Dec 11; 52(12):2578-2584en_US
dc.identifier.issn1432-0428en_US
dc.identifier.pmid19820914en_US
dc.identifier.doi10.1007/s00125-009-1524-3en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/42-
dc.description.abstractAIMS/HYPOTHESIS: Evidence from candidate gene studies suggests that obesity may modify genetic susceptibility to type 2 diabetes and dyslipidaemia. On an aggregate level, gene-obesity interactions are expected to result in different heritability estimates at different obesity levels. However, this hypothesis has never been tested. METHOD: The present study included 2,180 British female twins. BMI was used as an index of general obesity. Outcome measures were insulin sensitivity (indexed by quantitative insulin-sensitivity check index [QUICKI]) and fasting plasma lipid profile. Structural equation modelling was used to test whether BMI interacted with latent genetic and environmental effects to impact on the outcome measures. RESULTS: Genetic influences on triacylglycerol increased with BMI (p < 0.001) whereas the unique environmental influence on QUICKI decreased with BMI (p < 0.001), resulting in a higher heritability estimate for both measures at higher BMI levels. This was further illustrated by stratified analysis in twin pairs concordant for normal weight and twin pairs concordant for overweight. Heritability was 19 percentage points higher for triacylglycerol (p < 0.001) and 31 percentage points higher for QUICKI (p < 0.01) among twins concordant for overweight than among twins concordant for normal weight. BMI had no moderator effect on the latent genetic and environmental factors for total cholesterol and HDL-cholesterol. CONCLUSIONS/INTERPRETATION: Our results suggest that the expression of genes influencing triacylglycerol and insulin sensitivity can vary as a function of obesity status. The substantial increases in the genetic contribution to the total variance in insulin sensitivity and triacylglycerols at higher BMIs may prove extremely valuable in the search for candidate genes.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshBody Mass Indexen_US
dc.subject.meshBody Weighten_US
dc.subject.meshFemaleen_US
dc.subject.meshGreat Britainen_US
dc.subject.meshHumansen_US
dc.subject.meshInsulin / pharmacology / physiologyen_US
dc.subject.meshLipids / blooden_US
dc.subject.meshObesity / blood / genetics / physiopathologyen_US
dc.subject.meshTriglycerides / blood / metabolismen_US
dc.titleHeritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction.en_US
dc.typeJournal Articleen_US
dc.typeTwin Studyen_US
dc.identifier.pmcidPMC2776165en_US
dc.contributor.corporatenameGeorgia Institute for Prevention of Human Diseases and Accidentsen_US

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