Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression

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	Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression
	Li, YF; Dang, XL; Chen, R; Teng, ZW; Wang, JY; Li, SW; Yue, YY; Mitchell, BL; Zeng, Y; Yao, YG; Li, M; Liu, ZC; Yuan, YG; Li, T; Zhang, ZJ; Luo, XJ
	2025
发表期刊	Nat. Hum. Behav.
ISSN	2397-3374
卷号	9 期号:4
摘要	Deciphering the genetic architecture of depression is pivotal for characterizing the associated pathophysiological processes and development of new therapeutics. Here we conducted a cross-ancestry genome-wide meta-analysis on depression (416,437 cases and 1,308,758 controls) and identified 287 risk loci, of which 49 are new. Variant-level fine mapping prioritized potential causal variants and functional genomic analysis identified variants that regulate the binding of transcription factors. We validated that 80% of the identified functional variants are regulatory variants, and expression quantitative trait loci analysis uncovered the potential target genes regulated by the prioritized risk variants. Gene-level analysis, including transcriptome and proteome-wide association studies, colocalization and Mendelian randomization-based analyses, prioritized potential causal genes and drug targets. Gene prioritization analyses highlighted likely causal genes, including TMEM106B, CTNND1, AREL1 and so on. Pathway analysis indicated significant enrichment of depression risk genes in synapse-related pathways. Finally, knockdown of Tmem106b in mice resulted in depression-like behaviours, supporting the involvement of Tmem106b in depression. Our study identified new risk loci, likely causal variants and genes for depression, providing important insights into the genetic architecture of depression and potential therapeutic targets.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15207
专题	其他
推荐引用方式 GB/T 7714	Li, YF,Dang, XL,Chen, R,et al. Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression[J]. Nat. Hum. Behav.,2025,9(4).
APA	Li, YF.,Dang, XL.,Chen, R.,Teng, ZW.,Wang, JY.,...&Luo, XJ.(2025).Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression.Nat. Hum. Behav.,9(4).
MLA	Li, YF,et al."Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression".Nat. Hum. Behav. 9.4(2025).

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2026071465.pdf（2802KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文