对472,819名个体进行的多血统全基因组荟萃分析确定了32个新的银屑病风险基因座。

Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis.

作者信息

Zhang Min, Su Wenting, Deng Jiahui, Zhai Bin, Zhu Gaizhi, Gao Ran, Zeng Qi, Qiu Jinming, Bian Ziqing, Xiao He, Luan Guoming, Wang Renxi

机构信息

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.

Laboratory for Clinical Medicine, Capital Medical University, Beijing, China.

出版信息

J Transl Med. 2025 Jan 30;23(1):133. doi: 10.1186/s12967-024-06015-8.

DOI:10.1186/s12967-024-06015-8

PMID:39885523

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11783861/

Abstract

BACKGROUND

Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear.

METHODS

Here we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls.

RESULTS

We identified 74 genome-wide significant loci for psoriasis. Of 74 loci, 32 were novel psoriasis risk loci. Across 74 loci, 801 likely causal genes are indicated and 164 causal genes are prioritized. SNP-based heritability analyses demonstrated that common variants explain 15% of genetic risk for psoriasis. Gene-set analyses and the genetic correlation revealed that psoriasis-related genes have the positive correlations with autoimmune diseases such as ulcerative colitis, inflammatory bowel diseases, and Crohn's disease. Gene-drug interaction analysis suggested that psoriasis-associated genes overlapped with targets of current medications for psoriasis. Finally, we used the multi-ancestry meta-analysis to explore drug repurposing and the potential targets for psoriasis.

CONCLUSIONS

We identified 74 genome-wide significant loci for psoriasis. Based on 74 loci, we provided new biological insights to the etiology of psoriasis. Of clinical interest, we gave some hints for 76 potential targets and drug repurposing for psoriasis.

摘要

背景

银屑病是一种常见的慢性、复发性、免疫介导的疾病，累及皮肤或关节或两者。然而，对银屑病遗传易感性的深入了解仍不清楚。

方法

在此，我们对全基因组关联研究进行了最大规模的多血统荟萃分析，包括28869例银屑病病例和443950例健康对照。

结果

我们确定了74个全基因组显著的银屑病位点。在这74个位点中，32个是新的银屑病风险位点。在74个位点中，指出了801个可能的因果基因，并对164个因果基因进行了优先排序。基于单核苷酸多态性的遗传力分析表明，常见变异解释了银屑病遗传风险的15%。基因集分析和遗传相关性显示，银屑病相关基因与自身免疫性疾病如溃疡性结肠炎、炎症性肠病和克罗恩病呈正相关。基因-药物相互作用分析表明，银屑病相关基因与当前银屑病药物的靶点重叠。最后，我们使用多血统荟萃分析来探索银屑病的药物再利用和潜在靶点。