Bivariate genetic modelling of the response to an oral glucose tolerance challenge: a gene x environment interaction approach.
OBJECTIVE
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
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.
Liu
G F
GF
Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. g.liu@epi.umcg.nl
Riese
H
H
Spector
T D
TD
Mangino
M
M
O'Dell
S D
SD
Stolk
R P
RP
Snieder
H
H
D000328:Adult; D001786:Blood Glucose / Q000235:genetics; D015992:Body Mass Index; D004777:Environment; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D008962:Models, Theoretical; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
D001786:Blood Glucose; D007328:Insulin