New insights into causal relationship between serum lipids, obesity, and asthma: a Mendelian randomization study

Objective To identify causal risk factors for asthma using a Mendelian randomization (MR) approach.Methods Genetic variants associated with the exposures at the genome-wide significance level (p < 5 × 10 − 8) were obtained from corresponding genome-wide association studies. Summary-level statistical data for asthma were obtained from the UK Biobank (UKB) and the FinnGen Consortia. Univariate and multivariate MR analyses were performed to clarify causal relationships among obesity, serum lipids, and asthma. Meta-analyses were performed to combine UKB and FinnGen results using a fixed-effects modelResults In FinnGen, the odds for asthma increased for every 1-SD increase in body mass index (BMI; odds ratio [OR] 1.292, p = 1.34 × 10−7), together with body fat percentage (BF%; OR 1.449, p = 0.049), and total cholesterol level (OR = 0.949, p = 0.027). However, higher BMI and BF% were found to increase the risk for asthma in the multivariate MR analysis. In the UKB, the BMI results were replicated. Meta-analysis revealed that high-density lipoprotein cholesterol could also increase the risk for asthma, although there were no associations with other risk factors included in this study.Conclusion This MR study found that genetically predicted higher BF% and BMI could increase the risk for asthma and corroborated some risk factors for asthma from previous MR studies. Moreover, the results suggest that higher BMI and BF% could serve as independent risk factors for asthma.