Relationship among genetic variants, obesity traits and asthma in the Taiwan Biobank.

BACKGROUND AND OBJECTIVE: Obesity and asthma impose a heavy health and economic burden on millions of people around the world. The complex interaction between genetic traits and phenotypes caused the mechanism between obesity and asthma is still vague. This study investigates the relationship among obesity-related polygenic risk score (PRS), obesity phenotypes and the risk of having asthma. METHODS: This is a matched case-control study, with 4 controls (8288 non-asthmatic) for each case (2072 asthmatic). Data were obtained from the 2008-2015 Taiwan Biobank Database and linked to the 2000-2016 National Health Insurance Research Database. All participants were ≥30 years old with no history of cancer and had a complete questionnaire, as well as physical examination, genome-wide single nucleotide polymorphisms and clinical diagnosis data. Environmental exposure, PM2.5, was also considered. Multivariate adjusted ORs and 95% CIs were calculated using conditional logistic regression stratified by age and sex. Mediation analysis was also assessed, using a generalised linear model. RESULTS: We found that the obese phenotype was associated with significantly increased odds of asthma by approximately 26%. Four obesity-related PRS, including body mass index (OR=1.07 (1.01-1.13)), waist circumference (OR=1.10 (1.04-1.17)), central obesity as defined by waist-to-height ratio (OR=1.09 (1.03-1.15)) and general-central obesity (OR=1.06 (1.00-1.12)), were associated with increased odds of asthma. Additional independent risk factors for asthma included lower educational level, family history of asthma, certain chronic diseases and increased PM2.5 exposure. Obesity-related PRS is an indirect risk factor for asthma, the link being fully mediated by the trait of obesity. CONCLUSIONS: Obese phenotypes and obesity-related PRS are independent risk factors for having asthma in adults in the Taiwan Biobank. Overall, genetic risk for obesity increases the risk of asthma by affecting the obese phenotype.