Environmental Factor, October 2009, National Institute of Environmental Health Sciences
Genome-Wide Association Study Focuses on Asthma in Children
By Robin Mackar
A new genome-wide association study (GWAS) published August 28 in PLoS Genetics identified the chromosome 9q21.31 region as a novel candidate region for childhood asthma. Researchers from the NIEHS, the National Institute of Public Health (Mexico) and their collaborators at universities in the U.S. and the U.K. looked at over 500,000 variants across the genome in 492 Mexican children with asthma and their parents to identify genes that may influence asthma development.
"We know that asthma is a chronic childhood disease that is influenced by both genetic and environmental factors, but so far no genes have been definitively shown to influence asthma development, " said Stephanie London, M.D., Dr.P.H., principal investigator at NIEHS and senior author of the study. "By using new approaches that have emerged in the past two years, such as genome-wide association studies, we're able to home in on specific regions that might be involved in the disease process."
To date, there have been only a handful of genome-wide association studies, commonly called GWAS, focused on asthma. Genetic studies of asthma are very few in Hispanic populations, making this the first GWAS in Mexicans and one of the first to look at genetic variation in an asthma GWAS in any Hispanic population. The GWAS approach involves scanning for markers across the complete genome of many people to find genetic variations they have in common that are associated with a particular disease.
"This is a small study by GWAS standards, but it adds to the growing body of research in this area," said Dana Hancock, Ph.D., a postdoctoral fellow who worked with London to author the paper. The researchers add that NIEHS is now part of a consortium with other researchers on studies funded by the NIH who are using GWAS data to look at asthma. "Being part of the NIH consortium known as EVE allows us to combine information from individuals across many studies, and this larger sample size is a more powerful approach to identify genetic risk factors and their interactions with environmental risk factors and to characterize how they may influence susceptibility to disease," Hancock observed.
The paper also included an analysis that looked at ancestry in this Mexican population. The data suggest that chromosome 9q21.31 may underlie some of the differences in childhood asthma. Other studies have shown that different major ethnic groups have different rates of disease, but it remains unclear why Mexicans are more protected from asthma than other groups.
The chromosome 9q21.31 variants associated with childhood asthma in this study are located near the TLE4 gene, but London points out that further work is needed to decipher whether TLE4 or a nearby gene explains the signals from the chromosome 9q21.31 region.
"These studies are helping to increase our understanding of the gene-environment interactions and biological pathways that lead to disease, which provides new insights into prevention, as well as treatment interventions," said NIEHS Director Linda Birnbaum, Ph.D.
Citation: Hancock DB, Romieu I, Shi M, Sienra-Monge JJ, Wu H, Chiu GY, Li H, del Rio-Navarro BE, Willis-Owens SA, Weiss ST, Raby BA, Gao H, Eng C, Chapela R, Burchard EG, Tang H, Sullivan PF, London SJ. (http://www.ncbi.nlm.nih.gov/pubmed/19714205?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) 2009. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in Mexican children. PLoS Genet 5(8):e1000623. Epub Aug 28.
(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)