Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN 37614-1700, USA.
J Mol Neurosci. 2013 Jun;50(2):250-6. doi: 10.1007/s12031-012-9931-1. Epub 2012 Dec 11.
Major depression disorder (MDD) is a complex and chronic disease that ranks fourth as cause of disability worldwide. About 14 million adults in the USA are believed to have MDD, and an estimated 75 % attempt suicide making MDD a major public health problem. Neuroticism has been recognized as an endophenotype of MDD; however, few genome-wide association (GWA) analyses of neuroticism as a quantitative trait have been reported to date. The aim of this study is to identify genome-wide genetic variants affecting neuroticism using a European sample. A linear regression model was used to analyze the association with neuroticism as a continuous trait in the Netherlands Study of Depression and Anxiety and Netherlands Twin Registry population-based sample of 2,748 individuals with Perlegen 600K single nucleotide polymorphisms (SNPs). In addition, the neuroticism-associated genes/loci of the top 20 SNPs (p < 10⁻⁴) were examined with anti-social personality disorder (ASPD) in an Australian twin family study. Through GWA analysis, 32 neuroticism-associated SNPs (p < 10⁻⁴) were identified. The most significant association was observed with SNP rs4806846 within the TMPRSS9 gene (p = 7.79 × 10⁻⁶) at 19p13.3. The next best signal was in GRIN2B gene (rs220549, p = 1.05 × 10⁻⁵) at 12p12. In addition, several SNPs within GRIN2B showed borderline associations with ASPD in the Australian sample. In conclusion, these results provide a possible genetic basis for the association with neuroticism. Our findings provide a basis for replication in other populations to elucidate the potential role of these genetic variants in neuroticism and MDD along with a possible relationship between ASPD and neuroticism.
重度抑郁症（MDD）是一种复杂的慢性疾病，是全球导致残疾的第四大原因。据估计，美国有 1400 万成年人患有 MDD，大约 75%的人试图自杀，这使得 MDD 成为一个主要的公共卫生问题。神经质已被认为是 MDD 的一种内表型；然而，迄今为止，很少有关于神经质作为一种数量性状的全基因组关联（GWA）分析报道。本研究的目的是使用欧洲样本识别影响神经质的全基因组遗传变异。线性回归模型用于分析荷兰抑郁与焦虑研究和荷兰双胞胎登记处基于人群的样本中神经质作为连续特征的关联，该样本包含 2748 名个体，个体的 Perlegen 600K 单核苷酸多态性（SNP）数据。此外，还在澳大利亚双胞胎家族研究中，对前 20 个 SNP（p < 10⁻⁴）的神经质相关基因/位点与反社会人格障碍（ASPD）进行了检查。通过 GWA 分析，确定了 32 个神经质相关 SNP（p < 10⁻⁴）。最显著的关联是在 19p13.3 上 TMPRSS9 基因内的 SNP rs4806846（p = 7.79 × 10⁻⁶）。下一个最佳信号位于 12p12 上的 GRIN2B 基因（rs220549，p = 1.05 × 10⁻⁵）。此外，澳大利亚样本中几个 GRIN2B 内的 SNP 与 ASPD 呈边缘关联。总之，这些结果为神经质的关联提供了可能的遗传基础。我们的发现为在其他人群中进行复制提供了依据，以阐明这些遗传变异在神经质和 MDD 中的潜在作用，以及 ASPD 和神经质之间的可能关系。
