Birth weight is not causally associated with adult asthma: results from instrumental variable analyses

Abstract

The association between lower birth weight and childhood asthma is well established by observational studies. However, it remains unclear whether the influence of lower birth weight on asthma can persist into adulthood. Here, we conducted a Mendelian randomization analysis to assess the causal relationship of birth weight on the risk of adult asthma. Specifically, we carefully selected genetic instruments based on summary statistics obtained from large-scale genome-wide association meta-analyses of birth weight (up to ~160,000 individuals) and adult asthma (up to ~62,000 individuals). We performed Mendelian randomization using two separate approaches: a genetic risk score approach and a two-sample inverse-variance weighted (IVW) approach. With 37 genetic instruments for birth weight, we estimated the causal effect per one standard deviation (SD) change of birth weight to be an odds ratio (OR) of 1.00 (95% CI 0.98~1.03, p=0.737) using the genetic risk score method. We did not observe nonlinear relationship or gender difference for the estimated causal effect. In addition, with the IVW method, we estimated the causal effect of birth weight on adult asthma was observed (OR=1.02, 95% CI 0.84~1.24, p=0.813). Additionally, the iMAP method provides no additional genome-wide evidence supporting the causal effects of birth weight on adult asthma. The result of the IVW method was robust against various sensitivity analyses, and MR-PRESSO and the Egger regression showed that no instrument outliers and no horizontal pleiotropy were likely to bias the results. Overall, this Mendelian randomization study provides no evidence for the fetal origins of diseases hypothesis for adult asthma, implying that the impact of birth weight on asthma in years of children and adolescents does not persist into adult and previous findings may be biased by confounders.