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Multiethnic Risk for Lung Disease: Genetics and Smoking

Institution: University of Southern California
Investigator(s): Linda Polfus, PhD
Award Cycle: 2019 (Cycle 28) Grant #: 28KT-0001 Award: $990,000
Subject Area: Pulmonary Disease
Award Type: New Investigator Awards

Initial Award Abstract

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading health problems in the US and risk for these diseases are differential across race/ethnicity. In the Multiethnic Cohort (MEC), a long-standing ethnically diverse prospective cohort (>215,000 participants) established in the early 1990’s in California and Hawaii, we observed striking ethnic differences in African Americans and Native Hawaiians that are more susceptible to lung cancer than whites, Japanese Americans, and Latino smokers. Studies of the human genome’s association with lung cancer and COPD have identified 135 sites highly related to lung disease. Investigators have attempted to leverage genetic data to better identify those most at risk of lung disease, but these studies have been primarily conducted in whites. Here, we propose to use biospecimens and individual-level risk factor data from 47,000 MEC participants from five ethnic groups (including California’s most vulnerable non-white populations) to calculate a risk score comprised of the most significant genetic findings combined with risk factors to predict lung disease risk unique to an ethnic group. We hypothesize that the contributions of multiple genes interacting with the duration a person smoked cigarettes, better capture the lifetime risk of lung disease. This will help point to reasons why disease rates may differ amongst ethnic groups. First, we will characterize the ethnic specific genetic score reported in the literature and apply those to our MEC study data, which includes risk factors captured over 17 years, genetic information, and disease diagnosis to evaluate lung disease risk (e.g., lung cancer and COPD) as new cases develop over time (AIM 1); Second, we will estimate how much an ethnic group’s lung disease risk calculation is directly related to genetics and how much is due to smoking. We will also evaluate if our model is a better statistical model than other models previously reported (AIM 2). This study is highly unique as it would be the first to simultaneously develop and test genetic risk scores across lung disease in five ethnic groups. Findings from this work will help to improve our understanding of health disparities for these outcomes and provide ethnic specific risk measures useful for prevention.