Heritability of fasting glucose levels in a young genetically isolated population

Abstract

Aims/hypothesis: The heritability of fasting glucose levels in Northern European populations has been examined previously in twins and samples of small pedigrees. In this study the heritability of fasting plasma glucose (FPG) was estimated in participants in the Erasmus Rucphen Family study, who were members of a single pedigree from a young genetic isolate. We also studied the relationship between FPG and components of the metabolic syndrome.

Methods: FPG, lipid, blood pressure and body composition measurements were completed for 852 participants without diabetic medication. The most significant predictors of FPG were used as covariates in heritability estimation. The sibship effect, which is a composite of genetic dominance and shared early-life environmental effects, was included as a random effect.

Results: The age- and sex-adjusted heritability of log normal-transformed FPG was 36.6%. When further adjusted for metabolic risk factors, namely body composition parameters, systolic blood pressure, triglycerides and cholesterol: HDL ratio, the heritability estimate rose to 42.8%. After adjustment for the sibship effect, the additive component of heritability was estimated to be 28.3% (age- and sex-adjusted) and 24.9% (full model).

Conclusions/interpretation: Genes control a significant proportion of the variance in FPG levels. Adjustment for other metabolic risk factors did not substantially change the heritability estimate, which suggests that a large part of the variance in FPG levels is due to genes that act through pathways that are independent of those controlling body composition, blood pressure and lipid levels.