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东亚人群中哮喘、过敏性鼻炎和花粉症共同遗传位点的鉴定。

Identification of shared genetic loci for asthma, allergic rhinitis, and pollinosis in East Asians.

作者信息

Wang Dong, Liu Shuai, Wu Qinfeng, Jiang Yue, Zhang Chumeng, Ye Weiyi, Peng Bichen, Xie Haoran, Li Wen, Wang Yue, Zhi Lili, Chang Xiao, Shao Lei

机构信息

Jinan Engineering Polytechnic, Jinan, China.

Agricultural Products Quality and Safety Center of Jinan, Jinan, China.

出版信息

Sci Rep. 2025 Feb 19;15(1):6068. doi: 10.1038/s41598-025-90443-z.

Abstract

Asthma, allergic rhinitis, and pollinosis are prevalent respiratory conditions that often co-occur, suggesting common genetic and environmental causes. While significant progress has been made in identifying genetic loci in European populations, the genetic architecture in East Asian populations remains poorly understood. Using GWAS summary statistics from BioBank Japan, we performed multi-trait genome-wide association studies (MTAG) to quantify the genetic overlap among asthma, allergic rhinitis, and pollinosis in East Asians. Genetic correlation analysis revealed significant positive correlations among the three conditions, and stratified LDSC (Linkage Disequilibrium Score Regression) analysis identified heritability enrichments in Blood/Immune and Digestive tissues. We discovered novel pleiotropic loci at 9q32 and 10q25.2 specific to East Asians, with candidate gene expression analysis highlighting differential expression of AKNA, ATP6V1G1, and GPAM. These findings provide new insights into the shared genetic architecture and biological mechanisms underlying these conditions, advancing our understanding of their genetic determinants and identifying potential therapeutic targets.

摘要

哮喘、过敏性鼻炎和花粉症是常见的呼吸系统疾病,常常同时出现,这表明它们存在共同的遗传和环境病因。虽然在确定欧洲人群的基因位点方面已取得重大进展,但东亚人群的遗传结构仍知之甚少。我们利用日本生物银行的全基因组关联研究(GWAS)汇总统计数据,开展了多性状全基因组关联研究(MTAG),以量化东亚人群中哮喘、过敏性鼻炎和花粉症之间的遗传重叠情况。遗传相关性分析揭示了这三种疾病之间存在显著的正相关,分层连锁不平衡评分回归(LDSC)分析确定了血液/免疫组织和消化组织中的遗传力富集情况。我们在东亚人群特有的9q32和10q25.2发现了新的多效性位点,候选基因表达分析突出了AKNA、ATP6V1G1和GPAM的差异表达。这些发现为这些疾病潜在的共同遗传结构和生物学机制提供了新见解,增进了我们对其遗传决定因素的理解,并确定了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f29/11840148/079bb53c33e3/41598_2025_90443_Fig1_HTML.jpg

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