TY - JOUR T1 - Associations of BMI, fat mass and lean mass with childhood asthma: Mendelian randomization study JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - 3495 AU - Raquel Granell AU - John Henderson AU - David Evans AU - George Smith AU - Andy Ness AU - Sarah Lewis AU - Tom Palmer AU - Jonathan Sterne Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/3495.abstract N2 - Studies have reported associations between body mass index (BMI) and asthma in childhood, but it is difficult to exclude confounding and reverse causality as explanations. Genomewide association studies have identified 32 independent loci associated with BMI (Speliotes EK et al. 2010).We used Mendelian randomization to investigate the causal effect of BMI, fat mass and lean mass on childhood asthma.A weighted allele score was derived from 32 imputed SNPs. We multiplied the imputation weight of the risk allele by a SNP-specific weight as estimated in the reported meta-analysis by Speliotes et al., then averaged across SNPs. We estimated associations of the weighted allele score with BMI, fat mass, lean mass and asthma at age 7-7.5. The generalized method of moments was used to estimate causal (instrumental variable) risk ratios for the effect of BMI, fat and lean mass on asthma (Palmer TM et al. 2011).4835 children had complete data on 32 BMI-associated SNPs, asthma and BMI at 7-7.5 years. The weighted allele score was strongly associated with BMI (regression coefficient 2.22, 95% CI 1.76-2.67, p=2.3×10-21), fat mass (2.88, 2.35-3.42, p=2.0×10-25), lean mass (1.22, 0.80-1.64, p=1.6×10-8) and childhood asthma (risk ratio [RR] 2.56, 1.38-4.76, p=0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (1.16-2.07), p=0.003. This effect appeared stronger in girls (1.77, 1.13-2.77, p=0.01) than boys (1.40, 0.96-2.04, p=0.08). The estimated causal RRs for the effect of fat mass and lean mass on asthma were 1.41 (1.11-1.79), p=0.01 and 2.25 (1.23-4.11), p=0.01 respectively.Higher BMI, fat mass and lean mass in mid childhood cause increases in the risk of childhood asthma. ER -