Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
PLoS One. 2010 Jul 9;5(7):e11504. doi: 10.1371/journal.pone.0011504.
Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p < 10(-6)) and GPC6 showed suggestive evidence for interaction with age (p approximately = 10(-7)). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.
神经质是一种中度遗传的人格特质，被认为是患重度抑郁症、焦虑症和痴呆症的风险因素。我们在一个基于人群的神经质研究中对 2235 名参与者进行了全基因组关联研究，这是迄今为止针对神经质的最大关联研究。神经质通过艾森克人格问卷进行测量。经过质量控制，我们分析了 43 万个常染色体 SNPs，以及从 HapMap CEU 样本中高质量推断出的另外 120 万个 SNPs。我们发现人群分层的影响很小，用一个主成分进行了校正，并且存在一些不需要校正的隐性亲缘关系。NKAIN2 作为主要效应与神经质具有暗示性关联的证据（p < 10(-6))，GPC6 显示与年龄有交互作用的暗示性证据（p 约等于 10(-7))。我们发现了一个先前报道的关联（PDE4D）的支持，但未能复制其他最近的报告。这些结果表明，常见的 SNP 变异并没有强烈影响神经质。我们的研究有能力检测到几乎所有解释至少 2%遗传率的 SNP，因此我们的结果有效地排除了存在对神经质有重大影响的基因座的可能性。
