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Protein markers of diabetes discovered in an African American cohort

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posted on 2023-01-11, 18:39 authored by Zsu-Zsu Chen, Yan Gao, Michelle J. Keyes, Shuliang Deng, Michael Mi, Laurie A. Farrell, Dongxiao Shen, Usman A. Tahir, Daniel E. Cruz, Debby Ngo, Mark D. Benson, Jeremy M. Robbins, Adolfo Correa, James G. Wilson, Robert E. Gerszten

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 self-identified 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. 

Funding

Research in this manuscript was supported by the NIDDK with K23DK127073 to Z.C. and NHLBI with NHLBI with R01HL133870 and the TOPMed contract HHSN268201600034I to R.E.G. The Jackson Heart Study (JHS) is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I/HHSN26800001) and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I and HHSN268201800012I) contracts from the National Heart, Lung, and Blood Institute 1 and the National Institute for Minority Health and Health Disparities (NIMHD).

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