Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study

To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland.

Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance component model (SOLAR). In addition, family means of these traits and their distribution across families are calculated.

The strongest heritability for type 2 diabetes was seen in patients with age at onset 35–60 years (h ² = 0.69). However, including patients with onset up to 75 years dropped the h ² estimates to 0.31. Among quantitative traits, the highest h ² estimates in all individuals and in non-diabetic individuals were seen for lean body mass (h ² = 0.53–0.65), HDL-cholesterol (0.52–0.61) and suppression of NEFA during OGTT (0.63–0.76) followed by measures of insulin secretion (insulinogenic index [IG₃₀] = 0.41–0.50) and insulin action (insulin sensitivity index [ISI] = 0.37–0.40). In contrast, physical activity showed rather low heritability (0.16–0.18), whereas smoking showed strong heritability (0.57–0.59). Family means of these traits differed two- to fivefold between families belonging to the lowest and highest quartile of the trait (p < 0.00001).

To detect stronger genetic effects in type 2 diabetes, it seems reasonable to restrict inclusion of patients to those with age at onset 35–60 years. Sequencing of families with extreme quantitative traits could be an important next step in the dissection of the genetics of type 2 diabetes.