遗传建筑学
全基因组关联研究
重性抑郁障碍
遗传相关
共病
遗传关联
相关性
焦虑
数量性状位点
特质
遗传学
基因
生物
遗传变异
临床心理学
医学
单核苷酸多态性
精神科
基因型
心情
数学
程序设计语言
几何学
计算机科学
作者
Liwei Mei,Yan Gao,Min Chen,Xiao Zhang,Weihua Yue,Dai Zhang,Hao Yu
标识
DOI:10.1016/j.pnpbp.2021.110450
摘要
Major depressive disorders (MDDs) and anxiety and stress-related disorders (ASRDs) have overlapping symptoms and high rates of comorbidity. However, the underlying mechanisms remain largely unknown. Here, we aimed to examine whether MDD and ASRD share genetic risk factors utilizing recent large-scale genome-wide association studies (GWASs). To examine the genetic overlap between MDD and ASRD, we applied genetic correlation analysis to analyze GWAS summary statistics for MDD (16,823 cases and 25,632 controls) and ASRD (12,665 cases and 19,225 controls). We found positive and significant genetic correlations between MDD and ASRD (GNOVA: rho = 0.59, se = 0.01, P = 5.32 × 10-45). Our latent causal variable (LCV) analysis indicated the genetic correlation result from pleiotropic effects (gcp = -0.56, se = 0.31, Pgcp = 0.1). Based on pleiotropic enrichment, we performed a cross-trait meta-analysis of MDD and ASRD GWAS and fine-mapped the identified loci. In total, we identified 5 pleiotropic loci simultaneously associated with MDD and ASRD at P < 5 × 10-8. At the gene level, we further demonstrated that MDD- and ASRD-inferred gene expression overlapped across 48 tissues and highlighted the NUP210L gene as a potential mediator of the genetic correlation. Our study highlights a shared underlying genetic risk for MDD and ASRD, which may help to improve the understanding of high comorbidity and overlapping genetic mechanisms between the two traits.
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