PROJECT SUMMARY/ABSTRACT Hispanics/Latinos (H/L) are the largest minority ethnic group in the US. Despite low socioeconomic status, H/L have lower mortality than non-Hispanic whites (NHW) – the “Hispanic Paradox.” This survival advantage declines with time and generation, which has led to the proposition that erosion of healthful lifestyle habits and social resources combine with the cumulative stresses of immigration to degrade health. Longitudinal studies examining these factors are lacking. At the same time, there is evidence that the Hispanic Paradox may not apply to major diseases. H/L suffer a high burden of non-alcoholic fatty liver disease (NAFLD), including its more advanced form, non-alcoholic steatohepatitis (NASH), which is becoming the most common cause of liver transplant in the US. NASH has been difficult to study, however, because the diagnosis has depended on biopsy. While H/L also have a disproportionate burden of obesity and diabetes, this does not fully account for NAFLD. Meanwhile, discovery of two major genetic variants that interfere with hepatic lipid processing, but do not predispose to obesity or insulin resistance, has introduced the concept of “genetic NAFLD.” This may be of particular relevance to H/L, because one such variant is highly prevalent in various H/L heritage groups. Unlike NAFLD, prevalence of CVD is lower in H/L than NHW, but cardiac dysfunction and heart failure risk appear higher. Data from our group using partial MRI of the liver has linked hepatic fibrosis to myocardial fibrosis. Here we will parlay the opportunity for a third exam of the Hispanic Community Health Study/Study of Latinos (SOL), and the strengths of contrast MRI, to address important knowledge gaps in this diverse group. We plan to evaluate relations of nativity and duration of US residence with MRI-determined hepatic fibrosis and myocardial strain, while leveraging longitudinal assessments of lifestyle, psychosocial and sociocultural factors to assess their cumulative impact on these phenotypes, and to explore mediation of immigration and acculturation effects. We will also examine the contributions of visceral fat and low adiponectin levels, as well as genetic susceptibility, alone and in combination, to hepatic fibrosis. Last, we will evaluate the association between hepatic fibrosis and myocardial fibrosis, along with proinflammatory and procoagulant factors that may link the two disorders. This study will yield key insights into the Hispanic Paradox in NAFLD and CVD and their behavioral and psychosocial determinants; newly characterize the burden of hepatic fibrosis in H/L and its genetic underpinnings; and investigate the liver-heart axis and underlying pathways as a potentially serious threat to the health of this vulnerable ethnic group.