Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study
Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study
复制标题
DOI：
10.1007/s00125-011-2267-5
复制
发表时间：
2011-11-01
期刊：
影响因子：
8.2
通讯作者：
Groop, L.
中科院分区：
文献类型：
--
作者：
Almgren, P.;Lehtovirta, M.;Groop, L.
为了研究芬兰波特尼亚研究中的2型糖尿病及相关数量性状在家庭中的遗传度和熟悉度，采用方差成分模型(SOLAR)对不同年龄组的2型糖尿病患者以及942个家庭5810个个体的34个临床和代谢性状进行了调整，并对2型糖尿病的遗传度进行了估计。此外，还计算了这些性状的家系平均值及其在家庭中的分布。发病年龄在35-60岁(h(2)=0.69)的患者中，2型糖尿病的遗传力最强。然而，包括发病年龄长达75岁的患者，h(2)估计值降至0.31。在数量性状中，所有个体和非糖尿病个体的h(2)估计值最高的是瘦体重(h(2)=0.53-0.65)、高密度脂蛋白-胆固醇(0.52-0.61)和OGTT期间的NEFA抑制(0.63-0.76)，其次是胰岛素分泌(胰岛素生成指数[IG(30)]=0.41-0.50)和胰岛素作用(胰岛素敏感指数[ISI]=0.37-0.40)。相比之下，体力活动的遗传度较低(0.16-0.18)，而吸烟的遗传度较高(0.57-0.59)。这些性状的家系平均值在属于最低和最高四分位数的家系之间相差2-5倍(p<；0.00001)。为了检测2型糖尿病更强的遗传效应，似乎有理由将患者限制在发病年龄为35-60岁的人群中。对具有极端数量性状的家系进行测序可能是剖析2型糖尿病遗传学的重要下一步。
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.