Rocky 2022

Childhood asthma is the most common reason for hospitalization in early childhood. From epidemiological studies, it is evident that the prevalence is higher in boys than girls. After puberty, it is more prominent in women than men. The heritability of childhood asthma is estimated to be between 60 and 90%. This suggests that the genetic components driving the development of childhood asthma have a sex-specific effect. Yet, most association studies do not consider gender in their analysis.

In this project, a Bayesian logistic regression model with a variant-sex interaction term was developed in RStan to identify SNPs that have a sex-specific effect on childhood asthma. Discovery studies were conducted in a dataset of 1189 children with severe asthma (2-6 hospitalizations) from Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and 5094 non-asthmatic controls. Twenty variants have a posterior probability of interaction higher than 76%.

A subset of individuals with severe asthma (6+ hospitalizations, 372 individuals) suggests 17 variants with a posterior probability higher than 80% of having a sex interaction, of which two are found to be part of the genes IL1R1 and CLEC16A, known for being associated with asthma previously, and 4 of the top 9 interacting variants are expressed in lung tissue. Sex-stratified analysis confirms the sex-specific effect in both data sets.

Suggested variants do not replicate UK Biobank (5581 cases, 88094 controls), which might indicate that the definition of the asthma phenotype in both data sets is too different. Further replication is planned in the iPSCYH data set.