Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Diabetes Care. 2010 Feb;33(2):293-7. doi: 10.2337/dc09-0947. Epub 2009 Nov 10.
Our aim was to characterize familial risks for type 2 diabetes by the type and number of affected family members, including half-siblings, adoptees, and spouses, to quantify risks and estimate the contribution of environmental effect.
Families were identified from the Multigeneration Register, and type 2 diabetic patients were obtained from the Hospital Discharge Register. Standardized incidence ratios were calculated for offspring with type 2 diabetes whose family members were hospitalized for type 2 diabetes at ages >39 years compared with those lacking affected family members.
The number of hospitalized type 2 diabetic patients was 157,549. Among 27,895 offspring, 27.9% had a parent or sibling also hospitalized for type 2 diabetes. The familial relative risk (RR) ranged from 2.0 to >30, depending on the number and type of probands. The highest RRs of type 2 diabetes were found in individuals who had at least two siblings affected by type 2 diabetes, irrespective of the parental disease. Adoptees showed no risk from adopted parents.
The study, the largest yet published, showed that familial RRs varied by the number and type of affected family member. However, much of the familial clustering remains yet to be genetically explained. The high risk should be recognized in clinical genetic counseling. The data from adoptees confirmed the genetic basis of the familial associations, but those from half siblings and spouses suggested that a smaller part of familial clustering may be accounted for by environmental factors.
通过受影响家庭成员的类型和数量(包括同父异母或同母异父兄弟姐妹、领养子女和配偶)来描述 2 型糖尿病的家族风险,量化风险并估计环境效应的贡献。
从多代登记处中确定家庭,并从住院登记处获得 2 型糖尿病患者。与没有受影响家庭成员的患者相比,年龄 >39 岁时因 2 型糖尿病住院的患者的后代中患有 2 型糖尿病的标准化发病比(发病率比)进行了计算。
住院的 2 型糖尿病患者人数为 157,549 人。在 27,895 名后代中,27.9%的患者的父母或兄弟姐妹也因 2 型糖尿病住院。家族相对风险(RR)范围为 2.0 至 >30,具体取决于先证者的数量和类型。无论父母是否患病,至少有两个兄弟姐妹患有 2 型糖尿病的个体患 2 型糖尿病的 RR 最高。领养子女从领养父母那里没有患病风险。
该研究是迄今为止发表的最大规模的研究,表明家族 RR 随受影响家庭成员的数量和类型而变化。然而,大部分家族聚集仍有待遗传解释。在临床遗传咨询中应认识到这种高风险。领养子女的数据证实了家族关联的遗传基础,但同父异母或同母异父兄弟姐妹和配偶的数据表明,家族聚集的一小部分可能由环境因素引起。