Proteomics has been leveraged to study type 2 diabetes (T2D), but the majority of available data are from White participants. Here, we extend prior work by analyzing a large cohort of self-identified African Americans (AAs) in the Jackson Heart Study (JHS, n=1,313). We found 325 proteins associated with incident diabetes after adjusting for age, sex, and batch (FDR-q<0.05) measured using a single-stranded DNA aptamer affinity-based method in fasting plasma. A subset was independent of established markers of diabetes development pathways such as adiposity, glycemia, and/or insulin resistance—suggesting potential novel biological processes associated with disease development. Thirty-six associations remained significant after further adjustments for BMI, fasting plasma glucose (FPG), cholesterol levels, hypertension, statin use, and renal function. Twelve, including the top associations of complement factor H (CFH), formimidoyltransferase-cyclodeaminase (FTCD), serine/threonine-protein kinase 17B (STK17B), and high mobility group protein B1 (HMGB1), replicated in a meta-analysis of selfidentified White cohorts—the Framingham Heart Study and Malmö Diet and Cancer Study—supporting the generalizability of these biomarkers. A selection of these diabetes-associated proteins also improved risk prediction. Thus, we uncovered both novel and broadly generalizable associations by studying a diverse population, providing a more complete understanding of the diabetes associated proteome.

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