Many studies have reported an association between body mass index (BMI) and asthma that is stronger in girls than boys. However, it is difficult to prove the direction of causality. Genomewide association studies have identified a common variant in the FTO gene chromosome 16 that is associated with BMI and, in particular, fat mass. We used a Mendelian Randomization approach to assess evidence for a causal effect of BMI or fat mass on asthma.

A total of 4690 children enrolled in the ALSPAC birth cohort had measures of FTO genotype, BMI at age 7 years, asthma at age 7.5 (defined as a physician diagnosis together with a report of either wheezing or asthma treatment in the last year), and confounding variables. Fat and lean mass were measured at 9 years by dual energy x-ray absorptiometry (DEXA), in 4145 of these children. Associations with fat and lean mass were adjusted for height, height2 and gender. Fat mass was rescaled so that its standard deviation was similar to that for BMI.

There was clear evidence of associations of BMI (OR per kg/m2 1.07 (95% CI 1.02-1.11) and fat mass (OR per 500g 1.08 (1.04-1.13)) with asthma. The association with lean mass was weaker (OR per kg 1.05 (0.99-1.11)). Associations with BMI and lean mass appeared stronger in girls than boys, but the association with fat mass did not differ. BMI and fat mass, but not lean mass, were strongly associated with FTO genotype (Pless than 0.001). However, there was little evidence for an association of FTO with asthma (ORs 0.94 (0.78-1.14) for A:T and 1.19 (0.92,1.53) for A:A compared with T:T).

A Mendelian Randomization test did not support a causal link between asthma and fat mass or BMI. However, given that Mendelian Randomization tests have low power, these results do not exclude a causal effect. The discovery of further genes related to BMI and fat mass may increase the power of the Mendelian Randomization approach.

We therefore would like to investigate nine more BMI related SNPs that are now available in ALSPAC (see details of SNPs below).