G F Liu1, H Riese, T D Spector, M Mangino, S D O'Dell, R P Stolk, H Snieder. 1. Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. g.liu@epi.umcg.nl
Abstract
AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/ INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes.
AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/ INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes.
Authors: Timothy M Frayling; Nicholas J Timpson; Michael N Weedon; Eleftheria Zeggini; Rachel M Freathy; Cecilia M Lindgren; John R B Perry; Katherine S Elliott; Hana Lango; Nigel W Rayner; Beverley Shields; Lorna W Harries; Jeffrey C Barrett; Sian Ellard; Christopher J Groves; Bridget Knight; Ann-Marie Patch; Andrew R Ness; Shah Ebrahim; Debbie A Lawlor; Susan M Ring; Yoav Ben-Shlomo; Marjo-Riitta Jarvelin; Ulla Sovio; Amanda J Bennett; David Melzer; Luigi Ferrucci; Ruth J F Loos; Inês Barroso; Nicholas J Wareham; Fredrik Karpe; Katharine R Owen; Lon R Cardon; Mark Walker; Graham A Hitman; Colin N A Palmer; Alex S F Doney; Andrew D Morris; George Davey Smith; Andrew T Hattersley; Mark I McCarthy Journal: Science Date: 2007-04-12 Impact factor: 47.728