Abstract
The association between lower birth weight and childhood asthma is well established. However, it remains unclear whether the influence of lower birth weight on asthma can persist into adulthood. We conducted a Mendelian randomization analysis to assess the causal relationship of birth weight (~140,000 individuals) on the risk of adult asthma (~62,000 individuals). We estimated the causal effect of birth weight to be 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. With the inverse-variance weighted method, the causal effect of birth weight on adult asthma was estimated to be 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. Our results were robust against various sensitivity analyses, and MR-PRESSO and MR-Egger regression showed that no instrument outliers and no horizontal pleiotropy were likely to bias the results. Overall, our 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.
Highlights
Materials and MethodsData sources and selection of instrumental variables. We first obtained summary statistics of birth weight from the Early Growth Genetics (EGG) genome-wide association studies (GWASs) consortium study[39]
These single nucleotide polymorphisms (SNPs) are all robustly associated with birth weight (p < 5.00E-8)[39], and explain a total of 1.23% phenotypic variance of birth weight based on summary statistics
We find that no causal association exists between the genetically determined birth weight and adult asthma
Summary
Data sources and selection of instrumental variables. We first obtained summary statistics of birth weight from the Early Growth Genetics (EGG) GWAS consortium study[39]. For each of the remaining instrumental variables in turn, we obtained summary statistics for both birth weight and adult asthma in terms of effect allele, marginal effect size, and standard error as well as p value (Table 2). Where βjbirthweight is the obtained from the EGG estimated marginal SNP effect size of study[39], and SNPij is the individual-level birth weight for the jth instrumental variable genotype of the corresponding jth instrumental in the GERA study[44] and was coded to be 0, 1 and 2 in terms of the number of the effect allele which was matched with that in the EGG study. Besides the genetic risk score method, we performed a two-sample MR analysis to estimate the causal effect size of birth weight on adult asthma using summary statistics (Table 2). Additional ethical approval was not needed for our study
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