Social determinants of fatty liver disease and its racial/ethnic disparities: The Multi-Ethnic Study of Atherosclerosis

项目总结 肝病死亡率是美国最近预期寿命下降的一个关键因素。几十年来 研究表明，肝病在少数族裔和少数族裔中的负担不成比例 那些社会经济地位低的人。随着肥胖症的流行和酒精的增加 消费、脂肪肝(FLD)，包括非酒精性脂肪性肝病(NAFLD)和与酒精有关的 肝病(ALD)已成为影响数百万人的最常见的慢性肝病 在世界范围内，构成了一个重大的、日益严重的公共卫生问题。FLD流行病学主要集中在 个人层面的行为因素，如肥胖和饮酒，在FLD发展中的作用。 然而，以个人为重点的治疗和预防努力收效甚微。对许多慢性病患者来说 在疾病方面，大量文献记录了社会和自然环境如何影响人口健康。 相比之下，社会健康决定因素在FLD及其差异中的作用的经验证据是 非常有限。此外，目前解释FLD差异的范例主要集中在基因上 易感性(例如PNPLA3基因变异体)。 为了解决这些研究差距，该项目将测试个人和社区- 在一定程度上，社会决定因素影响FLD风险及其社会和种族/民族差异。为了检验这一假设， 我们建议获得并分析研究对象的肝脏脂肪和炎症的纵向测量。 动脉粥样硬化的多种族研究(MESA)，正在进行的最大规模的基于多种族人群的队列研究 涉及6个地区的6814名男性和女性(22%西班牙裔，38%白人，28%黑人，12%中国人) 美国不同的地区。MESA拥有最全面的社会经济纵向数据(包括个人 和社区层面)、心理社会、邻里物理和社会环境、环境、行为、 以及生物医学(包括遗传学)因素和健康结果，并进行长达21年的随访。我们的特定 目标是：1)通过10年来CT的变化来衡量FLD发病率的种族/民族差异。 测量了肝脏脂肪和肝酶，同时考虑了遗传变异。2)审视未来 个人层面的社会经济地位(SEP)和心理社会应激源与FLD发病率和 SEP和心理社会因素对FLD发病率的社会经济和种族/民族差异的贡献。 3)研究社区一级的社会和身体特征与FLD发病率的预期关联，以及 其在FLD发病率方面的种族/民族差异。4)研究社区层面的社会和身体特征的作用 通过测试基因与环境的交互作用来放大个体水平的遗传脆弱性 FLD的遗传变异和背景因素之间的关系。这个项目将构成最大、最严谨的 全面调查健康的社会决定因素在发展和进步中的作用 FLD及其差距的影响。

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.