Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during five years

Blood concentrations of triglycerides are influenced by genetic factors, as well as a number of environmental factors including adiposity and glucose homeostasis. The aim to investigate the association between a weighted serum triglyceride genetic risk score (wGRS) and changes in fasting serum triglyceride level over five years and to test whether the effect of the wGRS was modified by 5-year changes of adiposity, insulin resistance and lifestyle factors. A total of 3,474 non-diabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5-year follow-up physical examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years (per allele effect=1.3% (1.0;1.6); P=1.0*10(-17)). This triglyceride increasing effect of the wGRS interacted with changes in insulin resistance (Pint=1.5*10(-6)). This interaction suggested that the effect of the wGRS was stronger in individuals who became more insulin resistant over five years. In conclusion, our findings suggest that increased genetic risk load is associated with a larger increase in fasting serum triglyceride levels in non-diabetic individuals during five years of follow-up. This effect of the wGRS is accentuated by increasing insulin resistance.