小柯机器人

研究揭示创伤后应激障碍及其相关症状的全基因组关联
2021-01-31 22:24

美国耶鲁大学Joel Gelernter、加州大学圣迭戈分校Murray B. Stein等研究人员合作揭示创伤后应激障碍及其相关症状的全基因组关联。该项研究成果于2021年1月28日在线发表在《自然—遗传学》杂志上。

研究人员使用电子健康记录的创伤后应激障碍(PTSD)诊断和定量症状表型,对百万老兵计划(Million Veteran Program)中超过25万名欧洲(EUR)和非洲(AFR)血统的参与者进行了全基因组关联分析。通过应用全基因组多重测试校正,研究人员在欧洲病例对照分析中确定了三个重要基因座,并在定量症状分析中确定了15个基因座。

基因组结构方程模型表明,PTSD症状因子的紧密连贯性与遗传变异和独特的内在化(情绪-焦虑-神经病)因子共享。分隔的遗传力表明在几个皮质和皮质下区域富集,并且在这些区域中估算的遗传调控基因表达被用于鉴定潜在的药物重利用候选物。

这些结果证实了PTSD综合征的生物学一致性,揭示了它与焦虑症和抑郁症的关系,并为治疗提供了新的考量。 

附:英文原文

Title: Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program

Author: Murray B. Stein, Daniel F. Levey, Zhongshan Cheng, Frank R. Wendt, Kelly Harrington, Gita A. Pathak, Kelly Cho, Rachel Quaden, Krishnan Radhakrishnan, Matthew J. Girgenti, Yuk-Lam Anne Ho, Daniel Posner, Mihaela Aslan, Ronald S. Duman, Hongyu Zhao, Renato Polimanti, John Concato, Joel Gelernter

Issue&Volume: 2021-01-28

Abstract: We conducted genome-wide association analyses of over 250,000participants of European (EUR) and African (AFR) ancestry from the Million Veteran Program using electronic health record-validated post-traumatic stress disorder (PTSD) diagnosis and quantitative symptom phenotypes. Applying genome-wide multiple testing correction, we identified three significant loci in European case-control analyses and 15loci in quantitative symptom analyses. Genomic structural equation modeling indicated tight coherence of a PTSD symptom factor that shares genetic variance with a distinct internalizing (mood–anxiety–neuroticism) factor. Partitioned heritability indicated enrichment in several cortical and subcortical regions, and imputed genetically regulated gene expression in these regions was used to identify potential drug repositioning candidates. These results validate the biological coherence of the PTSD syndrome, inform its relationship to comorbid anxiety and depressive disorders and provide new considerations for treatment.

DOI: 10.1038/s41588-020-00767-x

Source: https://www.nature.com/articles/s41588-020-00767-x

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

分享到:

0