Department of Clinical Sciences, Diabetes and Endocrinology, CRC, Scania University Hospital Malmoe, Lund University, 20502 Malmoe, Sweden.
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.
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).
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.
目的/假设：研究芬兰 Botnia 研究中来自家庭的 2 型糖尿病及其相关定量特征的遗传性和家族性。
使用方差分量模型（SOLAR），为不同年龄组的 2 型糖尿病以及 942 个家庭的 5810 名个体中的 34 个临床和代谢特征，提供了调整性别、年龄和 BMI 后 2 型糖尿病的遗传率估计值。此外，还计算了这些特征的家族平均值及其在家族中的分布情况。
在发病年龄为 35-60 岁的患者中，2 型糖尿病的遗传力最强（h²=0.69）。然而，包括发病年龄可达 75 岁的患者，会将 h²估计值降至 0.31。在所有个体和非糖尿病个体中，瘦体重（h²=0.53-0.65）、高密度脂蛋白胆固醇（0.52-0.61）和 OGTT 期间 NEFA 的抑制（0.63-0.76）的 h²估计值最高，其次是胰岛素分泌的测量值（胰岛素原指数 [IG(30)]=0.41-0.50）和胰岛素作用（胰岛素敏感性指数 [ISI]=0.37-0.40）。相比之下，体力活动的遗传率相当低（0.16-0.18），而吸烟的遗传率很强（0.57-0.59）。属于特质最低和最高四分位数的家族之间，这些特征的家族平均值差异为 2 到 5 倍（p<0.00001）。
结论/解释：为了在 2 型糖尿病中检测到更强的遗传效应，将纳入的患者限制在发病年龄为 35-60 岁的范围内似乎是合理的。对具有极端定量特征的家族进行测序可能是解析 2 型糖尿病遗传的重要下一步。
