Heritability of metabolic syndrome traits in a large population-based sample

Abstract

Heritability estimates of metabolic syndrome traits vary widely across studies. Some studies have suggested that the contribution of genes may vary with age or sex. We estimated the heritability of 11 metabolic syndrome-related traits and height as a function of age and sex in a large population-based sample of twin families (N = 2,792-27,021, for different traits). A moderate-to-high heritability was found for all traits [from H(2) = 0.47 (insulin) to H(2) = 0.78 (BMI)]. The broad-sense heritability (H(2)) showed little variation between age groups in women; it differed somewhat more in men (e.g., for glucose, H(2) = 0.61 in young females, H(2) = 0.56 in older females, H(2) = 0.64 in young males, and H(2)= 0.27 in older males). While nonadditive genetic effects explained little variation in the younger subjects, nonadditive genetic effects became more important at a greater age. Our findings show that in an unselected sample (age range, ~18-98 years), the genetic contribution to individual differences in metabolic syndrome traits is moderate to large in both sexes and across age. Although the prevalence of the metabolic syndrome has greatly increased in the past decades due to lifestyle changes, our study indicates that most of the variation in metabolic syndrome traits between individuals is due to genetic differences.

Keywords: BMI; cardiovascular; cholesterol; diabetes; family study; genetics; lipids; obesity; sex difference; twin study.

Fig. 1.

Mean trait values stratified by age and sex. Age categories were defined based on the median age of subjects (young = subjects younger than the median and older = subjects older than the median). The median age was 35 years for SBP and DBP; 39 years for BMI; 40 years for HDL, LDL, total cholesterol, and triglycerides; and 41 for insulin, glucose, waist, and WHR. For height only, birth year (median = 1966) instead of age was used to define categories. Error bars represent standard deviations.

Fig. 2.

Heritability estimates stratified by age and sex. a² = narrow-sense heritability = V_A / V_P, d² = V_D / V_P, e² = V_E / V_P. Age categories were defined based on the median age of subjects (young = subjects younger than the median and older = subjects older than the median). The median age was 35 years for SBP and DBP; 39 years for BMI; 40 years for HDL, LDL, total cholesterol, and triglycerides; and 41 for insulin, glucose, waist, and WHR. For height only, birth year (median = 1966) instead of age was used to define categories. A: Young males. B: Older males. C: Young females. D: Older females.