Social determinants of fatty liver disease and its racial/ethnic disparities: The Multi-Ethnic Study of Atherosclerosis - PROJECT SUMMARY Liver disease mortality is a key contributor to recent declines in life expectancy in the US. Decades of research have demonstrated the disproportionate burden of liver disease among racial/ethnic minorities and those with low-socioeconomic position. With the ongoing epidemic of obesity, and the increase in alcohol consumption, fatty liver diseases (FLD), including non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), have become the most prevalent chronic liver conditions affecting millions of people worldwide, constituting a major and growing public health problem. FLD epidemiology has largely focused on the role of individual-level behavioral factors, such as obesity and alcohol consumption, in FLD development. However, individual-focused therapeutic and preventive efforts have had limited success. For many chronic diseases, abundant literature has documented how physical and socioeconomic environments pattern population health. In contrast, the empirical evidence of the role of these community-level factors on FLD and its disparities is extremely limited. Furthermore, the current paradigm to explain FLD disparities is heavily focused on genetic susceptibility (e.g. PNPLA3 gene variants). To address these research gaps, this project will test the novel hypothesis that individual and community-level factors influence FLD risk and their social and racial/ethnic disparities. To test this hypothesis, we propose to obtain and analyze longitudinal measures of liver fat and inflammation among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), the largest ongoing multi-racial population-based cohort study involving 6,814 men and women (22% Hispanic, 38% whites, 28% Blacks, 12% Chinese) from 6 geographically distinct areas of the US. MESA has the most comprehensive longitudinal data on socioeconomic (both individual and community level), psychosocial (e.g., chronic burden due to stress, depressive symptomatology), neighborhood physical environment (e.g., alcohol outlet density), environmental (e.g., heavy metals), behavioral, and biomedical (including genetics) factors and health outcomes with up to 21 years of follow-up. Our specific aims are: 1) Characterize racial/ethnic disparities in FLD incidence, as measured by 10-year changes in CT-measured liver fat and liver enzymes, while accounting for genetic variants. 2) Examine the prospective association of individual-level education and income and psychosocial stressors (e.g., chronic stress, depressive symptoms) with FLD incidence and socioeconomic and racial/ethnic disparities in FLD incidence. 3) Examine the prospective association of neighborhood-level socioeconomic and physical features (e.g., healthy food availability and alcohol outlets) with FLD incidence and its racial/ethnic disparities in FLD incidence. 4) Examine the role of neighborhood-level socioeconomic and physical features (e.g., healthy food availability and alcohol outlets) in magnifying individual-level genetic vulnerability by testing gene-by-environment interactions in the incidence of FLD between genetic variants and contextual factors. This project will constitute the largest, most rigorous and comprehensive investigation of the role of community level determinants of health in the development and progression of FLD and its disparities.
