Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Nat Neurosci. 2019 Sep;22(9):1394-1401. doi: 10.1038/s41593-019-0447-7. Epub 2019 Jul 29.
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 × 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.
创伤后应激障碍（PTSD）是退伍军人和平民都面临的一个主要问题，但它的病理生理学仍未得到很好的理解。我们进行了一项全基因组关联研究和生物信息学分析，该研究包括美国百万退伍军人计划中的 146660 名欧洲裔美国人和 19983 名非裔美国人，以确定与创伤性侵入性再体验相关的遗传风险因素，这是非 PTSD 最具特征性的症状群。在欧洲裔美国人中，确定了八个不同的显著区域。三个区域的值为 P < 5×10: CAMKV; 最接近 KANSL1 的 17 号染色体，但位于包括 CRHR1 在内的大型高度连锁不平衡区域内; 和 TCF4。关联与纹状体中间神经元的转录组特征丰富。在样本的非裔美国人队列中未观察到显著关联。在英国生物库数据中复制了欧洲裔美国人的结果。这些结果为 PTSD 的生物学提供了新的见解，这是一项功能强大的全基因组关联研究。
