Department of Biological Psychology, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands.
Amsterdam Public Health (APH) Research Institute, Amsterdam, The Netherlands.
Genes (Basel). 2021 Sep 26;12(10):1509. doi: 10.3390/genes12101509.
In recent years, evidence has accumulated with regard to the ubiquity of pleiotropy across the genome, and shared genetic etiology is thought to play a large role in the widespread comorbidity among psychiatric disorders and risk factors. Recent methods investigate pleiotropy by estimating genetic correlation from genome-wide association summary statistics. More comprehensive estimates can be derived from the known relatedness between genetic relatives. Analysis of extended twin pedigree data allows for the estimation of genetic correlation for additive and non-additive genetic effects, as well as a shared household effect. Here we conduct a series of bivariate genetic analyses in extended twin pedigree data on lifetime major depressive disorder (MDD) and three indicators of lifestyle, namely smoking behavior, physical inactivity, and obesity, decomposing phenotypic variance and covariance into genetic and environmental components. We analyze lifetime MDD and lifestyle data in a large multigenerational dataset of 19,496 individuals by variance component analysis in the 'Mendel' software. We find genetic correlations for MDD and smoking behavior ( = 0.249), physical inactivity ( = 0.161), body-mass index ( = 0.081), and obesity ( = 0.155), which were primarily driven by additive genetic effects. These outcomes provide evidence in favor of a shared genetic etiology between MDD and the lifestyle factors.
近年来，越来越多的证据表明基因的多效性普遍存在于整个基因组中，并且共享的遗传病因学被认为在精神障碍和风险因素之间广泛的共病中起着重要作用。最近的方法通过从全基因组关联汇总统计数据中估计遗传相关性来研究多效性。更全面的估计可以从遗传亲属之间已知的相关性中得出。扩展的双胞胎家系数据的分析允许估计加性和非加性遗传效应以及共享家庭效应的遗传相关性。在这里，我们在包含 19496 个人的大型多代数据集的扩展双胞胎家系数据中进行了一系列双变量遗传分析，对终生重度抑郁症（MDD）和三种生活方式指标（吸烟行为、身体活动不足和肥胖）的表型方差和协方差进行分解，这些指标分别为遗传和环境成分。我们通过“门德尔”软件中的方差成分分析，对终生 MDD 和生活方式数据进行了分析。我们发现 MDD 和吸烟行为（ = 0.249）、身体活动不足（ = 0.161）、体重指数（ = 0.081）和肥胖（ = 0.155）之间存在遗传相关性，这些相关性主要由加性遗传效应驱动。这些结果为 MDD 与生活方式因素之间存在共享遗传病因学提供了证据。
