ASTHMA is a complex, heterogenous condition and multiple genetic and environmental factors influence its manifestation. Advances in our sequencing technologies and capabilities are allowing genome-wide association studies (GWAS) to be more readily employed to identify these factors with greater confidence and across large cohorts of people. One such study has identified associations with potential clinical relevance in a multi-ethnic cohort of older adults.
Researchers from the Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA, conducted a GWAS using the the Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort. The study involved 68,623 asthmatics and non-asthmatics across four ethnic groups (non-Hispanic white, African–American, Asian, and Hispanic), making it one of the largest GWAS of asthma to date.
The genomic region IL18R1/IL1RL1 was highlighted from the association study as having common mutations that the researchers speculated introduce a new binding site for miR-452-5p, a member of the non-coding microRNA family capable of regulating gene expression through a variety of epigenetic means. Notably, miR-452-5p expression was up-regulated in airway epithelia samples in the asthmatic group compared to the control group. Sixteen additional loci were associated with asthma susceptibility in the non-Hispanic white group, each of which were derived from either the major histocompatibility complex gene HLA-DQA1 or the previously mentioned IL18R1/IL1R1 locus. Importantly, the lack of overlap across the ethnic groups suggest distinct asthmatic pathways exist in each.
“Identifying the genetic variants associated with asthma through GWAS is crucial for determining the genetic basis of asthma,” commented co-first author Joanne Sordillo, research scientist at the Harvard Pilgrim Health Care Institute. Considering these promising results, it is likely that future studies of this kind will incorporate various demographics or ethnicities to help further elucidate complex conditions such as asthma.