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 social and physical environments pattern population health.
In contrast, the empirical evidence of the role of social determinants of health with 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 social determinants 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, neighborhood physical and social environment, environmental, 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 socioeconomic position (SEP) and psychosocial stressors with FLD incidence and
the contribution of SEP and psychosocial factors to socioeconomic and racial/ethnic disparities in FLD incidence.
3) Examine the prospective association of community-level social and physical features with FLD incidence and
its racial/ethnic disparities in FLD incidence. 4) Examine the role of community-level social and physical features
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 social determinants of health in the development and progression
of FLD and its disparities.
