孟德尔随机化
哮喘
遗传流行病学
观察研究
医学
内科学
全基因组关联研究
遗传关联
多效性
胆固醇
流行病学
生物
遗传学
单核苷酸多态性
基因型
基因
遗传变异
表型
作者
Yi‐Shian Liu,Yu‐Chun Lin,Meng‐Chih Lin,Chao‐Chien Wu,Tsu‐Nai Wang
摘要
Abstract Background Observational studies and meta‐analyses have indicated associations between blood lipid profiles and asthma. However, the causal association is unknown. Therefore, this study investigated the causal relationship between blood lipid profiles and asthma using bidirectional Mendelian randomization analysis. Methods and materials Our analyses were performed using individual data from the Taiwan Biobank and summary statistics from the Asian Genetic Epidemiology Network (AGEN). The causal estimates between all genetic variants, exposures of interest and asthma were calculated using an inverse‐variance weighted method based on Taiwan Biobank data from 24,853 participants (mean age, 48.8 years; 49.8% women). Sensitivity analyses, including the weighted median, MR Egger regression, MR‐PRESSO, mode‐based estimate, contamination mixture methods, and leave‐one‐out analysis, were applied to validate the results and detect pleiotropy. Results In the inverse‐variance weighted (IVW) analyses, we found evidence of a significant causal effect of an increased level of low‐density lipoprotein cholesterol on asthma risk ( β IVW = 1.338, p = 0.001). A genetically decreased level of high‐density lipoprotein cholesterol was also associated with asthma risk ( β IVW = −0.338, p = 0.01). We also found that an increased level of total cholesterol was associated with an increased risk of asthma ( β IVW = 1.343, p = 0.001). Several sensitivity analyses generated consistent findings. We did not find evidence to support the causality between asthma and blood lipid profiles in either direction. Conclusion Our results supported the causal relationship between higher levels of LDL cholesterol and total cholesterol and lower levels of HDL cholesterol with an increased risk of asthma.
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