Late-breaking abstract: Gene environment interaction analysis of obesity and asthma

Background Asthma and obesity are common diseases with considerable impact on public health. Prospective studies showed that obesity is a risk factor for developing asthma and a causal relation has been proposed. However, there is limited evidence for the existence of shared genetic effects and it is not yet clear how obesity and genetic factors jointly influence the risk of developing asthma. Objective We sought to determine whether obesity (body mass index of 30 or greater) modifies the risk of developing asthma and to assess whether there is evidence for a causal relation linking the genetic risk of developing obesity with asthma. Methods The analyses were performed in genotyped individuals of two northern Finland birth cohorts. The discovery set (NFBC1966) and the in silico replication set (NFBC1986) comprised a sample of 4182 and 1441 individuals. The presence of asthma was determined by self-report of a physician diagnosis of asthma, and body mass index (BMI) was measured at time of clinical examination (at 31 and 16 years old respectively). Sixty SNPs previously associated with asthma or obesity from the GWAS catalogue were analysed. The gene environment interactions were formally tested with a full interaction model using logistic regression. The significant interactions (Pl0.05) found in the discovery dataset were meta-analysed with results of the replication set using fixed and random effects model. Results We prioritized six significant (Pl0.05) SNP interactions in the discovery set for replication (Fig. 1). Only one of the prioritized loci was previously associated with obesity (BMI). After meta-analysis with the replication set, we identified one directionally consistent interaction with obesity (P l 6.5x10-3) in rs2786098 near DENND1B, a SNP previously associated with asthma (Fig. 2). After meta-analysis, we did not find significant or directionally consistent interactions in SNPs previously associated with BMI or Obesity. Conclusion Our limited dataset suggests that obesity modifies the genetic risk of developing asthma. We did not found evidence for the hypothesis that obesity causes asthma.