On the Genetic Determinants of Asthma and Obesity

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DESCRIPTION (provided by applicant): The prevalence of obesity and asthma over the last two decades has reached epidemic proportions in the United States: more than a third of the U.S. population meets the clinical definition of obesity, and 11.2% will be diagnosed with asthma during their lifetimes. These conditions create an exorbitant public health burden. Together, their costs exceed $100 billion each year. Because these diseases are so prevalent, any improvement in treatment or prevention will substantially reduce healthcare costs and ease the public health burden. Although these diseases are influenced by environmental factors, research suggests that obesity and asthma are complex disorders that have genetic etiologies, with heritability estimates of 75% and 81%, respectively. But the genetic etiologies for asthma and obesity have only been studied independently, despite evidence from more than 20 epidemiological studies that suggests asthma is positively associated with preexisting obesity and that this relationship may be due in part to shared genetic determinants. Identifying genetic variants that influence both asthma and obesity promises to improve treatment and prevention on two fronts, thereby more effectively relieving the burden on public health. Our central hypothesis is that there are common genetic determinants for asthma and obesity. In this proposal we seek to identify these common genetic variants. Using genome-wide association study (GWAS) data, we will identify genetic associations with asthma and obesity using data from the Childhood Asthma Management Program (CAMP) study which consists of 422 parent-offspring trios. We will then replicate the top 200 associations in three Independent and ethnically diverse cohorts using a two phase approach. First we will genotype and analyze 200 single nucleotide polymorphisms (SNPs) In a Costa Rican cohort of 611 parent-offspring trios. We will then identify the 50 SNPs with the strongest associations. In the second phase we will genotype and analyze these 50 SNPs in two cohorts: 1) Crimson Caucasian: a sample of 2,000 asthmatic cases and 2,000 controls; and 2) Crimson African American: a sample of 1,000 asthmatic cases and 1,000 controls. Once we identify a set of SNPs that are consistently associated with asthma and obesity, we will determine the causal pathway behind the observed associations.