PROJECT SUMMARY Racial/ethnic disparities in infectious disease burden are common and can exacerbate existing social inequalities. Beyond the question of justice, health disparities have major economic consequences that can affect everyone in society. Previous studies have established the role of both environmental factors (e.g. healthcare access, socioeconomic status, lifestyle, and structural racism, to name a few) and human genetic factors in susceptibility to infectious diseases. However, systematic and comprehensive assessment of both sociodemographic and genetic factors that underlie ethnic/racial disparities in infectious disease is lacking. Filling this gap is important for both clinical care and public health. To this end, here we will leverage the genetic, electronic health records, and survey data from the All of US biobank to test the hypothesis that human genetic factors can contribute to racial/ethnic disparities in infectious disease burden independently of sociodemographic risk factors through the following aims: Aim 1: To identify demographic, socioeconomic, behavioral, and environmental factors that contribute to racial/ethnic disparities in infectious disease prevalence. In this aim, we will perform a comprehensive assessment of 227 demographic, socioeconomic, behavioral, and environmental variables, collected through All of US surveys, on the prevalence of 336 infectious disease phenotypes across fine-scale, genetically-defined population communities. At the end of this aim, we will know which infectious diseases are enriched or depleted in which fine-scale racial/ethnic communities and which demographic, socioeconomic, behavioral, and environmental variables are the main contributors to these disparities. Aim 2: To identify human genetic factors that contribute to racial/ethnic disparities in infectious disease prevalence. In this aim, we will perform in-depth analyses of genetic variants that can be associated with infectious disease prevalence. We will use complementary approaches to assess common and rare genetic variants. This aim will lead to the discovery of novel infectious disease susceptibility loci and risk variants. We will perform in silico functional analysis to gain insight to the function of these variants. In the short term, this study will result in identifying sociodemographic and genetic risk factors that underlie racial/ethnic disparities in infectious diseases and understanding their relative contribution to disease prevalence. Moreover, this project enhances our understanding of infectious disease biology and the genetic factors that affect interindividual variability in susceptibility to specific pathogens. In the long term, the results of this project can help the development of new public health policies or new diagnostic tests or drugs for infectious diseases.

NARRATIVE The project proposed here is relevant to public health for two reasons. First, it can guide the development of more equitable public health policies for infectious diseases. Second, it can lead to the discovery of novel biomarkers or drugs for infectious diseases which in turn can reduce the burden of infectious diseases.