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

Diabetologia. 2011 Nov;54(11):2811-9. doi: 10.1007/s00125-011-2267-5. Epub 2011 Aug 9.


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

Methods: 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.

Results: 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 [IG(30)] = 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).

Conclusions/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Body Mass Index
  • Cholesterol, HDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Family Health*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Finland / epidemiology
  • Genetic Predisposition to Disease*
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance
  • Male
  • Middle Aged
  • Models, Genetic
  • Motor Activity
  • Risk
  • Smoking / genetics
  • Young Adult


  • Cholesterol, HDL
  • Fatty Acids, Nonesterified