Revisiting the Links Between Asthma and the Psychosis Spectrum: shared molecular mechanisms

Epidemiological studies suggest associations of asthma with the psychosis spectrum (psychotic experiences, bipolar disorder, schizophrenia), but the mechanisms underlying these associations remain unclear. We examined the relationship between asthma and psychosis-related outcomes using observational cohort, polygenic score, and Mendelian randomization (MR) analyses, and assessed the possibility of shared genetic underpinnings between these traits using genetic colocalisation. Results from a UK population-based prospective birth cohort suggest that asthma at age 7 and polygenic risk for asthma are associated with psychotic experiences in early adulthood. Results from two-sample MR analyses do not support causal relationships of genetic liability to asthma with bipolar disorder or schizophrenia. Instead, genetic correlation and colocalization analyses point to the presence of shared genetic aetiology between the conditions. We identified 8 genomic regions with potentially shared causal genes between asthma and bipolar disorder or asthma and schizophrenia. Using genetically predicted mRNA expression in condition-relevant tissues (brain and lung), we identified 16 genes shared between conditions, which include FADS1, SLC4A10, BDH2, and CISD2. Our results suggest that population-level associations of asthma with psychosis spectrum conditions could be due to shared molecular mechanisms involving fatty acid metabolism, ion channel activity, and iron homeostasis.