Investigating the shared genetic architecture between post-traumatic stress disorder and neurodegenerative diseases: a large-scale genomewide cross-trait analysis

作者：Yi‐Ming Shi, Tao Zhao, Lequn Peng, Peng Wang, Xiaomeng Huang, Fan Xu, Yongle Tan, Shanyu Peng, Ting Xiong, Yang Bai, Xiaodan Liu, Changfa Wei, Wei Zhang, Huang Ding · 发表于：International Journal of Surgery · 年份：2025 · DOI：10.1097/js9.0000000000004347 · 被引用次数：1 · 研究领域：Genetic Associations and Epidemiology、Genetic Mapping and Diversity in Plants and Animals、Bioinformatics and Genomic Networks

BACKGROUND: Post-traumatic stress disorder (PTSD), the most prevalent psychopathological consequence following traumatic events, profoundly impacts human life amidst global societal pressures. Emerging twin and family studies suggest that individuals with stress-related disorders face an elevated risk of neurodegenerative diseases, yet the genetic underpinnings of this association remain poorly understood. METHODS: Here, we present a comprehensive framework elucidating this genetic basis. Using bivariate causal mixture models (MiXeR), we quantified polygenic overlap between PTSD (N = 1,280,933) and four neurodegenerative phenotypes (N = 115,803- 487,511), leveraging summary statistics from the largest PTSD genome-wide association study to date. Conditional/conjunction false discovery rate (FDR) analysis identified shared genomic loci. RESULTS: MiXeR revealed considerable genetic variant sharing between neurodegenerative diseases and PTSD. Subsequent conjunction FDR analysis pinpointed 15 distinct shared loci. ρ-HESS local genetic correlation analysis identified seven significant local genetic correlations, with Chr6: 61,880,512-63,552,888 emerging as the most significant shared locus between PTSD and Alzheimer's disease. Cross-trait analyses using MTAG and CPASSOC identified 174 PTSD risk loci associated with at least one psychiatric disorder. Protein-coding genes mapped to known and novel shared loci exhibited specific spatial developmental trajectories. Through a framework ...