期刊
DIABETOLOGIA
卷 54, 期 11, 页码 2811-2819出版社
SPRINGER
DOI: 10.1007/s00125-011-2267-5
关键词
Families; Heritability; Quantitative traits; Type 2 diabetes
资金
- Sigrid Juselius Foundation
- Folkhalsan Research Foundation
- Swedish Research Council
- Linne grant
- EXODIAB
- EU
- Novo Nordisk Foundation
- Swedish Diabetes Research Foundation
- Finnish Diabetes Research Foundation
- Foundation for Life and Health in Finland
- Helsinki University Central Hospital Research Foundation
- Ollqvist Foundation
- Soderberg Foundation
- Municipal Heath Care Center and Hospital in Jakobstad
- Health Care Centers in Vasa, Narpes, Malax and Korsholm
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 [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). 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.
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