Genetic Epidemiology of Asthma and Allergic Diseases

Asthma and allergic diseases represent a group of complex disorders in which inherited genetic variation interacts with environmental exposures to shape individual susceptibility. Over the past two decades, large-scale genome-wide association studies have uncovered dozens of risk loci that collectively explain a modest but growing proportion of disease heritability. Many asthma-associated variants reside in non-coding regions and alter gene regulation rather than protein sequence. Integrative approaches combining transcriptomic, epigenomic and chromatin-interaction data have begun to link these variants to functional elements such as enhancers and promoters in airway epithelial or immune cells. Across populations of diverse ancestry, there is both shared and population-specific architecture, underscoring the importance of representation beyond European cohorts. Advances in expression quantitative trait locus mapping and Mendelian randomisation have prioritised candidate causal genes, many of which lie in pathways controlling type 2 inflammation, T cell differentiation and airway remodelling. The identification of low-frequency protective and risk alleles further illuminates novel targets for therapeutic intervention. Together, these developments have refined our understanding of how genetic variation shapes the onset, severity and persistence of asthma and related allergic conditions, paving the way for risk stratification and precision approaches to prevention and treatment.

Research from Nature Portfolio

Recent studies have leveraged biobank-scale datasets to map genetic susceptibility to asthma and allied conditions. A large genome-wide analysis identified over forty novel loci shared across multiple upper respiratory and atopic phenotypes, revealing non-synonymous variants that influence sinonasal versus pharyngeal disease susceptibility and highlighting convergent pathways with asthma and atopic dermatitis. Finemapping and phenome-wide analyses demonstrated that distinct gene networks underlie type 2 high inflammation in different airway compartments. Another investigation combined genome-wide association with transcriptome-wide association and Mendelian randomisation to prioritise nearly five hundred blood-regulated genes as causal for asthma. Key drivers include established targets such as IL4R and TSLP, alongside novel candidates implicated in immune regulation. Functional enrichment emphasised open-chromatin regions in immune cells, and druggability assessments pointed to both validated and emerging therapeutic targets. These efforts underscore the power of multi-omic integration to translate genetic associations into mechanistic insights and potential interventions.

Genetic Epidemiology of Asthma and Allergic Diseases publication trend

The graph below shows the total number of articles in genetic epidemiology of asthma and allergic diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Genome-wide association study (GWAS): A hypothesis-free search for common genetic variants across the genome that are statistically associated with a trait or disease.

Expression quantitative trait locus (eQTL): A genomic region containing variant(s) that influence the expression level of one or more genes.

Transcriptome-wide association study (TWAS): An analytical approach that integrates GWAS and gene expression data to identify genes whose predicted expression is associated with disease risk.

Enhancer: A non-coding DNA element that can increase transcription of target genes, often in a cell-type-specific manner via chromatin looping.

Single nucleotide polymorphism (SNP): A single base-pair change in the genome that is common in the population and may influence phenotype or disease risk.

References

1. Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation. Nature Communications (2023).
2. Decoding the genetic and epigenetic basis of asthma. Allergy (2023).
3. A distal enhancer of GATA3 regulates Th2 differentiation and allergic inflammation. Proceedings of the National Academy of Sciences of the United States of America (2024).
4. Prioritization of candidate causal genes for asthma in susceptibility loci derived from UK Biobank. Communications Biology (2021).
5. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations. Nature Communications (2019).
6. Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma. Nature Communications (2015).