Abstract：
Although 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.
摘要：
尽管有报道称一系列血液特征与甲型流感（H1N1）pdm09（H1N1pdm09）疾病的严重程度有关，其潜在的因果关系和生物学机制尚不清楚.本研究旨在使用两个样本孟德尔随机分析来研究血液性状与H1N1pdm09之间的因果关系。根据我们的内部全基因组关联研究（GWAS）的数据，该研究涉及H1N1pdm09疾病严重程度（Ncase[severe]=70，Ncontrol[mild]=95）和日本Biobank44个血液性状的GWAS摘要（N=12303-143658），我们确定了血液性状对严重的H1N1N1pdm09的潜在因果效应.逆方差加权法分析揭示了谷草转氨酶降低的显著因果效应(AST，β=-3.212,p=0.019),低密度脂蛋白胆固醇（LDL-C，β=-1.372，p=0.045），和嗜碱性粒细胞计数(Baso，β=-1.638，p=0.047）严重的H1N1N1pdm09疾病。此外,多基因风险评分分析进一步证实了这些血液性状与严重的H1N1pdm09疾病之间的遗传重叠。这项研究提供了证据表明较低水平的AST，LDL-C,巴索患有严重的H1N1N1pdm09病，可能为重症流感患者确定新的治疗靶点。
