Genome-Wide Association Study Identifies Asthma Gene

Frank D. Gilliland, M.D., Ph.D. and W. James Gauderman, Ph.D.,
Keck School of Medicine, University of Southern California
NIEHS Grants P01ES011627 and P30ES007048

A multi-center study identified two single nucleotide polymorphisms of a gene known as phosphodiesterase 4D or PDE4D as an asthma susceptibility gene in a large genome-wide association study. PDE4D is a regulator of airway smooth muscle contractility and medications targeted towards inhibition of the enzyme have been developed to treat asthma.

Over 300 million people, or approximately one out of 20, in the world are affected by asthma. Over 20 million people in the U.S. alone have asthma. The economic impact of this disease from lost work productivity as a result of the disease or from caring for a child with asthma is staggering. Previous studies have identified over 40 genes associated with asthma.

A genome-wide association study is an approach that involves scanning markers across the complete genome of many people to find genetic variations they have in common associated with a particular disease. Once the genetic associations are identified, the information is used to develop better strategies to detect, treat, and prevent disease. These studies have proven particularly useful in finding genetic variations that contribute to complex diseases such as asthma, cancer, diabetes, heart disease, and mental illnesses.

Two single nucleotide polymorphisms proved to be highly statistically significant with respect to asthma in a combined population of over 18,000 white and Hispanic subjects. Further study of the polymorphisms of PDE4D will lead to an improved understanding of the gene’s role in asthma and the efficacy of PDE4D inhibitors in treating asthma.

Citation: Himes BE, Hunninghake GM, Baurley JW, Rafaels NM, Sleiman P, Strachan DP, Wilk JB, Willis-Owen SA, Klanderman B, Lasky-Su J, Lazarus R, Murphy AJ, Soto-Quiros ME, Avila L, Beaty T, Mathias RA, Ruczinski I, Barnes KC, Celedón JC, Cookson WO,Gauderman WJ, Gilliland FD, Hakonarson H, Lange C, Moffatt MF, O'Connor GT, Raby BA, Silverman EK, Weiss ST. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. Am J Hum Genet. 2009 May;84(5):581-93.