Multi-trait genetic analysis of asthma and eosinophils uncovers pleiotropic loci in East Asians

Lili Zhi, Qiwen Zheng, Yue Jiang, Lu Yu, Linzehao Li, Yingchao Song, Bichen Peng, Chumeng Zhang, Hengxuan Jiang, Ren Li, Frank Mentch, Joseph Glessner, Peilin Jia, Hua Tang (), Hakon Hakonarson () and Xiao Chang ()
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Lili Zhi: The First Affiliated Hospital of Shandong First Medical University
Qiwen Zheng: Chinese Academy of Sciences and China National Center for Bioinformation
Yue Jiang: Shandong First Medical University
Lu Yu: Shandong First Medical University
Linzehao Li: Shandong First Medical University
Yingchao Song: Shandong First Medical University
Bichen Peng: Shandong First Medical University
Chumeng Zhang: Shandong First Medical University
Hengxuan Jiang: Shandong First Medical University
Ren Li: Shandong First Medical University
Frank Mentch: Children’s Hospital of Philadelphia
Joseph Glessner: Children’s Hospital of Philadelphia
Peilin Jia: Chinese Academy of Sciences and China National Center for Bioinformation
Hua Tang: Shandong First Medical University
Hakon Hakonarson: Children’s Hospital of Philadelphia
Xiao Chang: The First Affiliated Hospital of Shandong First Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-60405-0

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