Background: Obesity is increasingly recognized as a possible risk factor for childhood asthma. The underlying mechanisms remain unclear but seem to involve a shared genetic background.

Objective: To enlighten the association between genetic susceptibility to high BMI and asthma, infections, and other asthma-related traits during early childhood.

Methods: Data was obtained from the two ongoing COPSAC mother-child cohorts. A polygenic risk score (PRS) for high BMI was calculated for each child. Data for replication was obtained from two large-scale cohorts, iPSYCH and COPSACsevere, where data on hospitalization for asthma and infections were obtained from the National Patient Register. 

Results: The BMI PRS was significantly associated with number of asthmatic exacerbations (IRR 1.42, 95% CI 1.15; 1.76, p=0.001) and lower respiratory tract infections (LRTI) (IRR 1.21, 1.09; 1.34, p=0.0003) at age 0-3 years. These findings were not mediated through the child?s current BMI. The BMI PRS was not associated with asthma to age 6. The results replicated in iPSYCH, where high BMI PRS increased risk of hospitalization for bronchitis/asthma (OR 1.11, 95% CI 1.09; 1.13, p<0.0001) and LRTI (OR 1.04, 95% CI 1.03, 1.07, p<0.0001), and in COPSACsevere, where high BMI PRS increased risk of asthma with recurrent hospitalizations (OR 1.09, 95% CI 1.02; 1.16, p=0.01) at age 0-6 years.

Conclusion: The genetic susceptibility to high BMI was associated with asthmatic exacerbations and LRTI in early childhood independently of the child?s current BMI, indicating a common genetic background rather than obesity itself. These results increase the understanding of the relationship between obesity and asthma.