Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA.
Department of African American Studies, Virginia Commonwealth University, Richmond, VA, USA.
Eur J Psychotraumatol. 2023;14(1):2178762. doi: 10.1080/20008066.2023.2178762.
Although trauma exposure (TE) is a transdiagnostic risk factor for many psychiatric disorders, not everyone who experiences TE develops a psychiatric disorder. Resilience may explain this heterogeneity; thus, it is critical to understand the etiologic underpinnings of resilience. The present study sought to examine the genetic underpinnings of psychiatric resilience using genome-wide association studies (GWAS), genome-wide complex trait analysis (GCTA), and polygenic risk score (PRS) analyses. Participants were 6,634 trauma exposed college students attending a diverse, public university in the Mid Atlantic. GWAS and GCTA analyses were conducted, and using GWAS summary statistics from large genetic consortia, PRS analyses examined the shared genetic risk between resilience and various phenotypes. Results demonstrate that nine single-nucleotide polymorphisms (SNPs) met the suggestive of significance threshold, heritability estimates for resilience were non-significant, and that there is genetic overlap between resilience and AD, as well as resilience and PTSD. Mixed findings from the present study suggest additional research to elucidate the etiological underpinnings of resilience, ideally with larger samples less biased by variables such as heterogeneity (i.e. clinical vs. population based) and population stratification. Genetic investigations of resilience have the potential to elucidate the molecular bases of stress-related psychopathology, suggesting new avenues for prevention and intervention efforts.
尽管创伤暴露(TE)是许多精神障碍的一种跨诊断风险因素,但并非每个经历过 TE 的人都会患上精神障碍。韧性可能解释了这种异质性;因此,了解韧性的病因基础至关重要。本研究旨在使用全基因组关联研究(GWAS)、全基因组复杂性状分析(GCTA)和多基因风险评分(PRS)分析来研究精神韧性的遗传基础。参与者是 6634 名在大西洋中部的一所多元化公立大学就读的创伤暴露大学生。进行了 GWAS 和 GCTA 分析,并使用来自大型遗传联盟的 GWAS 汇总统计数据,PRS 分析研究了韧性与各种表型之间的共同遗传风险。结果表明,有九个单核苷酸多态性(SNP)达到了显著意义的阈值,韧性的遗传估计值没有统计学意义,韧性与 AD 以及韧性与 PTSD 之间存在遗传重叠。本研究的混合结果表明,需要进一步研究以阐明韧性的病因基础,理想情况下使用更大的样本,减少异质性(即临床与人群)和群体分层等变量的偏差。韧性的遗传研究有可能阐明与应激相关的精神病理学的分子基础,为预防和干预措施提供新途径。