Introduction: Obesity/body mass index (BMI) is one of the leading risk factors of cardiovascular disease (CVD) in both African American and non-Hispanic white populations. Identifying the range of factors that lead to the persistent and pronounced differences in the BMI of populations is critical for developing effective strategies for reducing these inequalities and ultimately reducing the incidence of CVD. It is posited that these differences arise from the interplay between both biological (genes) and social factors (environments). Standard approaches to this complex problem of incorporating “bio-social” data remain fractured; examining only biological, or only social determinants of the diseases/risk factors in question. This paradigm is not effective in uncovering the origins of diseases that arise from the relationships between multiple systems. By incorporating both biological and sociological data, we seek to better understand the health disparities underlying obesity. Hypotheses: We hypothesize that there will be gene regions associated with BMI in both African and non-Hispanic whites, but not necessarily the same regions across ethnicity. We expect stronger associations in each ethnicity with gene regions defined from meta-analysis of that ethnicity. We hypothesize that low socioeconomic position, lower levels of social support and higher levels of anger, ongoing stressful life events, and depressive symptoms will modify the effects of genetic predictors on BMI. Methods: We used novel, gene region-based analysis methods (Sequence Kernel Association Testing and Gene-Environment Set Association Test) with gene regions identified from 103 known obesity loci (97 from published GWAS meta-analysis in European ancestry and 6 from African ancestry), to examine the effect of gene regions on BMI in up to 3,000 African Americans and up to 12,000 non-Hispanic whites from the Health and Retirement Study. We also investigated the modification of these gene regions’ effects on BMI by social and psychosocial environment and compared across ethnicity. Results and Conclusions: Preliminary results indicate strong gene-region associations in African Americans with several genes including GPRC5B (p=0.024), SH2B1 (p=0.016) and TNNI3K (p=0.004) as well as statistically significant associations between BMI and social/psychosocial variables (bivariate p<0.01 for anger, social support, socioeconomic position, stressful life events and depression scores in non-Hispanic whites; depression score in African Americans). Gene-region results in the non-Hispanic whites and interaction results are forthcoming. In conclusion, investigating gene-by-psychosocial and gene-by-socioeconomic interactions for one of the most important risk factors for chronic diseases in older adults could help motivate new bridges to be built between biological and social scientists.