Largest, Diverse Genome-Wide Association Study Links Loci to Asthma Risk

All risk factors for asthma come down to some form of environmental exposure and genetic predisposition, but the impact of the latter is not well understood. A large, genome-wide association study (GWAS), covering an ethnically diverse population, has found new loci that impacts asthma susceptibility in adults.

“This study contributes novel associations with potential functional relevance for asthma susceptibility in older adults of diverse racial backgrounds and represents one of the largest multiethnic GWASs of asthma to date,” investigators wrote.

The World Health Organization (WHO) estimates that about 235 million people worldwide have asthma. Because asthma is highly inheritable, research into the genetic origins of the disease is gaining steam. So far, 5 asthma genes have been identified, including DPP10, GRPA, and SPINK5, whose expressions create changes in the epithelium.

The hope is that findings will eventually lead to new therapies, more complete and efficient ways to diagnose asthma, and help identify environmental factors that protect against asthma.

Investigators—led by Amber Dahlin, PhD, MMSc, John Ziniti, MS, and Ann Chen Wu, MD, MPH, of the Channing Division of Network Medicine at Brigham and Women’s Hospital and Harvard Medical School—conducted an asthma GWAS using the Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort.

Investigators did not respond to requests for comment at the time of publication.

Participants totaled 68,623, including both asthma case and controls. Four racial groups were self-reported: non-Hispanic white, African American, Asian, and Hispanic.

Results showed that single nucleotide polymorphism (SNPs) within the MHC II region of chromosome 6 and the IL-1RL1/IL-18R1 region of chromosome 2 are linked to asthma risk in adults of non-Hispanic white ancestry. In those of Asian ancestry, asthma risk was associated with SNPs in 2 oxidative stress pathways: FOXRED2 and TXN2.

In addition, this study is the first GWAS to identify specific collagen and cadherin genes, COL25A1, COL3A1, and CDH7, as possible contenders for asthma risk in those of African American descent.

There is no overlap of asthma associations across ethnic groups. Investigators noted 1 reason could be the lack of data to detect the same genetic associations across ethnic subgroups because of low sample size for minority subjects and discrepancy in minor allele frequencies.

Dahlin and colleagues concluded the study findings contributed novel associations with potential functional relevance for asthma susceptibility in older, racially diverse adults. Additionally, it now represents 1 of the largest multiethnic GWASs of asthma.

“Collectively, these analyses replicated previously reported top asthma GWAS findings as well as increased the significance threshold for many of these associations, in addition to expanding the list of novel SNPs that are strongly associated with asthma risk,” investigators said.

The study, “Large-scale, multiethnic genome-wide association study identifies novel loci contributing to asthma susceptibility in adults,” was published online in Journal of Allergy and Clinical Immunology.