MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK.
Psychol Med. 2013 Sep;43(9):1965-71. doi: 10.1017/S0033291712002589. Epub 2012 Dec 14.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies. Method We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This 'heritability' was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10-8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R 2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
尽管通常认为应激性生活事件(SLEs)是外部环境应激源,但双胞胎研究报告了 SLEs 的一个显著可遗传部分。
我们研究了 2578 个人的全基因组关联研究(GWAS)中常见遗传变异标记的 SLEs 的方差。全基因组复杂性状分析(GCTA)用于估计单核苷酸多态性(SNP)标记的表型方差。我们还对 SLEs 的数量进行了 GWAS,并研究了兄弟姐妹之间的相关性。
SLEs 的 SNP 可解释相当大的变异比例(30%,p=0.04)。当将事件分为依存或独立事件时,两者都能解释相同数量的变异。这种“遗传力”部分受到神经质和精神病特质的人格测量的混淆。对 SLEs 总数的全基因组关联研究显示出一个 SNP 达到了全基因组显著水平(p=4×10-8),尽管在单独的样本中没有得到复制。利用 744 名个体的现有兄弟姐妹数据,我们还发现 SLEs 中存在显著的正相关,R 2=0.08(p=0.03)。
这些结果从分子数据为环境测量报告的遗传力提供了独立验证,并表明这种遗传力部分归因于常见变异和人格的混杂效应。