Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in >165,000 US veterans
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DOI：
10.1038/s41593-019-0447-7
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发表时间：
2019-09-01
影响因子：
25
通讯作者：
Stein, Murray B.
中科院分区：
文献类型：
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作者：
Gelernter, Joel;Sun, Ning;Stein, Murray B.
创伤后应激障碍（PTSD）是退伍军人和平民中的一个主要问题，但其病理生理学仍然知之甚少。我们进行了一项全基因组关联研究和生物信息学分析，其中包括美国百万退伍军人计划中的146，660名欧洲裔美国人和19，983名非洲裔美国人，以确定与创伤侵入性再体验相关的遗传风险因素，这是PTSD最具特征的症状群。在欧洲裔美国人中，确定了八个不同的重要区域。三个区域的P值< 5 × 10（-10）：CAMKV;染色体17最接近KANSL 1，但在一个大的高连锁不平衡区域，也包括CRHR 1;和TCF 4。协会丰富的纹状体中型多刺神经元的转录组学配置文件。在样本的非裔美国人队列中没有观察到显著的相关性。欧洲裔美国人的结果在英国生物库数据中得到了复制。这些结果为PTSD的生物学提供了新的见解，这是一项强有力的全基因组关联研究。
Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood. We performed a genome-wide association study and bioinformatic analyses, which included 146,660 European Americans and 19,983 African Americans in the US Million Veteran Program, to identify genetic risk factors relevant to intrusive reexperiencing of trauma, which is the most characteristic symptom cluster of PTSD. In European Americans, eight distinct significant regions were identified. Three regions had values of P < 5 x10(-10): CAMKV; chromosome 17 closest to KANSL1, but within a large high linkage disequilibrium region that also includes CRHR1; and TCF4. Associations were enriched with respect to the transcriptomic profiles of striatal medium spiny neurons. No significant associations were observed in the African American cohort of the sample. Results in European Americans were replicated in the UK Biobank data. These results provide new insights into the biology of PTSD in a well-powered genome-wide association study.