Genetic Admixture and Pulmonary Function Decline

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DESCRIPTION (provided by applicant): Pulmonary function decline occurs with advanced age; however, the rate of decline varies by race/ethnicity and sex. In the United States, lower lung function is greatest among African Americans compared to whites and Mexican Americans. Pulmonary function decline is a complex disease resulting from the interaction of genetic and environmental factors. African Americans are considered to be admixed and share varying proportions of African, Amerindian and European ancestry. The mixed ancestry of African Americans provides unique opportunities in epidemiologic studies of complex traits and may be useful in untangling gene-environment interactions in disease susceptibility. The goal of this proposal is to identify genetic factors associated with reduced pulmonary function and pulmonary function decline among African Americans and examine whether observed genetic associations are modified by tobacco smoke exposure. This research will leverage existing genotyping and epidemiologic data from the Health, Aging, & Body Composition Study, a large longitudinal cohort study examining functional decline in older populations. Genetic ancestry will be estimated using ancestry informative markers and associations between genetic ancestry and reduced lung function and lung function decline will be examined. This research will provide important insight into the genetics of lung function and the impact of gene-environment interactions on racial/ethnic differences in lung function among African Americans. The following specific aims are proposed: Aim 1) To determine the association between genetic ancestry and reduced lung function and lung function decline over time. Aim 2) To perform admixture mapping to identify genetic loci associated with reduced lung function and lung function decline. Aim 3) To examine whether admixture modifies the association between tobacco smoke exposure and lung function. Lay Summary: Older adults have a high prevalence of comorbid diseases and limitations in lung airflow are often unrecognized. Identification of genes that affect pulmonary decline can identify new targets for drug treatments and lead to the development of important clinical tests. This study seeks to find genes of European or African origin that cause changes in the respiratory health of African Americans.