Causal relationship between blood traits and severe influenza A(H1N1)pdm09 infection in East Asian: A Mendelian randomization study

Author:

Wang Fuxiang1ORCID,Bian Shengzhe1,Zhou Wudi1,Liu Siyang1,Shu Yuelong12ORCID,Chen Yongkun3ORCID

Affiliation:

1. School of Public Health (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen People's Republic of China

2. Key Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing People's Republic of China

3. Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Basic Medical Sciences, Shenzhen University Medical School Shenzhen University Shenzhen People's Republic of China

Abstract

AbstractAlthough a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two‐sample Mendelian randomization analysis. Based on the data from our in‐house genome‐wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303–143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, β = −3.212, p = 0.019), low‐density‐lipoprotein cholesterol (LDL‐C, β = −1.372, p = 0.045), and basophil counts (Baso, β = −1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL‐C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.

Publisher

Wiley

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