Zhi Lili, Zheng Qiwen, Jiang Yue, Yu Lu, Li Linzehao, Song Yingchao, Peng Bichen, Zhang Chumeng, Jiang Hengxuan, Li Ren, Mentch Frank, Glessner Joseph, Jia Peilin, Tang Hua, Hakonarson Hakon, Chang Xiao
Department of Allergy, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
Nat Commun. 2025 May 31;16(1):5081. doi: 10.1038/s41467-025-60405-0.
Asthma is a prevalent respiratory condition with over 100 genetic loci identified through genome-wide association studies (GWAS). However, the genetic basis of asthma in East Asians remains underexplored. To address this, we performed a comprehensive analysis of shared genetic mechanisms between asthma and white blood cell (WBC) traits in East Asians, aiming to identify potential pleiotropic loci. Using linkage disequilibrium score regression (LDSC), we identified a significant genetic correlation between asthma and eosinophil count, further supported by Mendelian randomization (MR) analysis. A multi-trait analysis of GWAS (MTAG) uncovered 52 genome-wide significant loci, including 31 previously unreported loci specific to East Asians. Notably, we discovered a missense variant (rs75326924) in the CD36 gene that exhibits increased expression in lymphocytes and type 2 innate lymphoid cell (ILC2)-enriched cells in asthma patients, confirmed by flow cytometry. Proteomic profiling demonstrated downregulation of immune-related proteins such as Interleukin-7, Oncostatin M, and VEGFA in carriers of rs75326924, a variant previously associated with CD36 deficiency. Our findings provide insights into genetic loci and candidate genes underlying asthma in East Asians, offering potential targets for therapeutic interventions tailored to this population.
哮喘是一种常见的呼吸道疾病，通过全基因组关联研究（GWAS）已确定了100多个基因位点。然而，东亚人群哮喘的遗传基础仍未得到充分探索。为了解决这一问题，我们对东亚人群哮喘与白细胞（WBC）特征之间的共享遗传机制进行了全面分析，旨在确定潜在的多效性基因位点。使用连锁不平衡评分回归（LDSC），我们发现哮喘与嗜酸性粒细胞计数之间存在显著的遗传相关性，孟德尔随机化（MR）分析进一步支持了这一结果。全基因组关联研究的多性状分析（MTAG）发现了52个全基因组显著位点，其中包括31个以前未报道的东亚人群特有的位点。值得注意的是，我们在CD36基因中发现了一个错义变体（rs75326924），通过流式细胞术证实，该变体在哮喘患者的淋巴细胞和富含2型固有淋巴细胞（ILC2）的细胞中表达增加。蛋白质组学分析表明，rs75326924携带者中白细胞介素-�、制瘤素M和血管内皮生长因子A等免疫相关蛋白表达下调，该变体以前与CD36缺乏有关。我们的研究结果为东亚人群哮喘的遗传位点和候选基因提供了见解，为针对该人群的治疗干预提供了潜在靶点。
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