325-OR: Genetic and Socioeconomic Factors Are Independently Associated with Type 2 Diabetes

Abstract

Genetics and socioeconomic status (SES) are key drivers of increased type 2 diabetes (T2D) risk, but the extent to which they impact disease in an additive or non-additive manner is unknown. We examined T2D prevalence using cross-sectional electronic health record (EHR) data from 27,771 participants of European ancestry in the Mass General Brigham Biobank. A polygenic score for T2D was derived using a previously published globally expanded score (gePS). Multiple area-based socioeconomic risk estimates were evaluated (including deprivation indices and a machine learning model incorporating hundreds of census variables) with similar impact on T2D risk; here, an individual’s estimated SES risk was defined as the percent of residents in their census tract with less than high school education. T2D status was derived using a machine-learning algorithm validated by expert chart review to have 90% positive predictive value. The age and sex-adjusted odds of T2D was 1.72 (95% CI 1.63-1.81, p<0.001) per SD increase of T2D gePS and 1.36 (95% CI 1.31-1.42, p<0.001) per SD increase in socioeconomic risk. In a combined model of gePS and socioeconomic risk, these associations persisted, with no evidence of interaction. Persons in the highest quintile of both genetic and socioeconomic risk had an almost 3-fold risk of T2D compared to those of middle quintile risk for both (OR 2.67, 95% CI 2.08-3.44, p<0.001). Notably, the T2D risk of individuals in the highest quintile of genetic risk but lowest quintile of socioeconomic risk was indistinguishable from that of those in the middle quintile for both risk factors (OR 1.13, 95% CI 0.85-1.51). These data provide evidence for the independent associations of genetic risk and SES with T2D and suggest that living in a community with high SES is associated with reduced T2D risk, even among those at increased genetic risk. Our findings raise the hypothesis that interventions targeted at specific elements of SES, such as education, may reduce risk of T2D in those with high genetic risk. Disclosure S. Cromer: Employee; Spouse/Partner; Johnson & Johnson Medical Devices Companies. C. M. Lakhani: Consultant; Self; xy. ai. J. M. Mercader: None. T. Majarian: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. A. Manning: Employee; Spouse/Partner; Emulate, Inc, Stock/Shareholder; Spouse/Partner; Invitae. J. Merino: None. M. Udler: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007028)