Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Sci Adv. 2022 Apr 22;8(16):eabl4602. doi: 10.1126/sciadv.abl4602.
Coronary artery disease (CAD) remains the leading cause of death despite scientific advances. Elucidating shared CAD/pneumonia pathways may reveal novel insights regarding CAD pathways. We performed genome-wide pleiotropy analyses of CAD and pneumonia, examined the causal effects of the expression of genes near independently replicated SNPs and interacting genes with CAD and pneumonia, and tested interactions between disruptive coding mutations of each pleiotropic gene and smoking status on CAD and pneumonia risks. Identified pleiotropic SNPs were annotated to and . Increased expression across tissues consistently showed decreased risk for CAD and increased risk for pneumonia; increased expression showed increased risk for CAD and decreased risk for pneumonia. We similarly observed opposing CAD/pneumonia effects for . Reduced expression conferred a reduced CAD risk without increased pneumonia risk only among never-smokers. Genetic immune-inflammatory axes of CAD linked to respiratory infections implicate and , and related genes.
尽管科学取得了进步，但冠心病（CAD）仍然是主要的死亡原因。阐明 CAD/肺炎的共同途径可能会为 CAD 途径提供新的见解。我们对 CAD 和肺炎进行了全基因组的多效性分析，研究了在 CAD 和肺炎附近独立复制的 SNP 和相互作用的基因表达的因果效应，以及每种多效性基因的破坏性编码突变与吸烟状态之间对 CAD 和肺炎风险的相互作用。鉴定的多效性 SNP 被注释到 和 。在所有组织中表达增加都一致地降低了 CAD 的风险，增加了肺炎的风险； 表达增加则增加了 CAD 的风险，降低了肺炎的风险。我们同样观察到了 对 CAD/肺炎的相反影响。仅在从不吸烟者中， 表达减少会降低 CAD 的风险，但不会增加肺炎的风险。与呼吸道感染相关的 CAD 遗传免疫炎症轴涉及 和 以及相关基因。
