Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, China.
Hum Genet. 2021 Sep;140(9):1267-1281. doi: 10.1007/s00439-021-02288-x. Epub 2021 May 11.
We investigated the relationship between neuroticism and 16 mental and 18 physical traits using summary results of genome-wide association studies for these traits. LD score regression was used to investigate genetic correlations between neuroticism and the 34 health outcomes. Mendelian randomization was performed to investigate mutual causal relationships between neuroticism and the 34 health outcomes. Neuroticism genetically correlates with a majority of health-related traits and confers causal effects on 12 mental traits (major depressive disorder (MDD), insomnia, subjective well-being (SWB, negatively), schizophrenia, attention-deficit/hyperactivity disorder, alcohol dependence, loneliness, anorexia nervosa, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, and psychiatric disorders) and two physical diseases (cardiovascular disease and hypertensive disease). Conversely, MDD, SWB, and insomnia have a causal effect on neuroticism. We highlighted key genes contributing to the causal associations between neuroticism and MDD, including RBFOX1, RERE, SOX5, and TCF4, and those contributing to the causal associations between neuroticism and cardiovascular diseases, including MAD1L1, ARNTL, RERE, and SOX6. The present study indicates that genetic variation mediates the causal influences of neuroticism on mental health and cardiovascular diseases.
我们使用这些特征的全基因组关联研究的汇总结果来研究神经质与 16 种心理和 18 种身体特征之间的关系。使用 LD 分数回归来研究神经质与 34 种健康结果之间的遗传相关性。进行孟德尔随机化以研究神经质与 34 种健康结果之间的相互因果关系。神经质与大多数与健康相关的特征具有遗传相关性，并对 12 种心理特征（重度抑郁症（MDD）、失眠、主观幸福感（SWB，负相关）、精神分裂症、注意力缺陷/多动障碍、酒精依赖、孤独、神经性厌食症、焦虑症、双相情感障碍、强迫症和精神障碍）和两种身体疾病（心血管疾病和高血压疾病）产生因果影响。相反，MDD、SWB 和失眠对神经质有因果影响。我们强调了神经质与 MDD 之间的因果关联以及神经质与心血管疾病之间的因果关联的关键基因，包括 RBFOX1、RERE、SOX5 和 TCF4，以及神经质与心血管疾病之间的因果关联的关键基因，包括 MAD1L1、ARNTL、RERE 和 SOX6。本研究表明，遗传变异介导了神经质对心理健康和心血管疾病的因果影响。
