Large-scale proteomics to identify novel biomarkers linking social determinants of health to heart failure risk
Adverse social determinants of health (SDOH) associate with greater heart failure (HF) risk. Among 9879 community-based participants of the Atherosclerosis Risk in Communities (ARIC) cohort study, we assessed 4955 plasma proteins using an aptamer-based platform (SomaLogic). We derived an SDOH factor comprising income, education, and area deprivation index (ADI) in Black and white participants. Proteins associated with this factor at Bonferroni significance were tested for associations with incident HF using multivariable Cox proportional hazard models. Among Black participants, 36 proteins were associated with both the SDOH factor and incident HF, 126 were among white participants, and 12 were shared between race strata. Eight of these demonstrated significant mediation effect in causal mediation models. Key results were replicated in 49,396 participants in UK Biobank. Mendelian randomization and colocalization suggested a potentially causal effect of C1q tumor necrosis factor-related protein 1 (C1QTNF1), an adiponectin paralog, on HF. We demonstrate protein biomarkers associated with SDOH burden and HF risk.
Authors
- Chiadi E. Ndumele (ORCID: https://orcid.org/0000-0002-1603-282X)
- Rani Zierath
- Diego Ramonfaur (ORCID: https://orcid.org/0000-0003-3884-149X)
- Kenneth R. Butler (ORCID: https://orcid.org/0000-0003-3198-8835)
- Amil M. Shah (ORCID: https://orcid.org/0000-0003-1056-4451)
- Josef Coresh (ORCID: https://orcid.org/0000-0002-4598-0669)
- Yimin Yang (ORCID: https://orcid.org/0000-0003-2745-9498)
- Anna Kucharska‐Newton (ORCID: https://orcid.org/0000-0001-9864-467X)
- James S. Floyd (ORCID: https://orcid.org/0000-0002-0365-9041)
- Tammy Leonard (ORCID: https://orcid.org/0000-0002-8621-9358)
- Tiffany M. Powell‐Wiley (ORCID: https://orcid.org/0000-0001-9488-4131)
- Bing Yu (ORCID: https://orcid.org/0000-0003-4818-1077)
- Keenan A. Walker (ORCID: https://orcid.org/0000-0002-5989-9853)
- Michelle C. Odden (ORCID: https://orcid.org/0000-0002-5974-3648)
- Victoria Lamberson (ORCID: https://orcid.org/0000-0003-2760-5053)
- Nrupen Bhavsar
- Brian Claggett
- Ganga Bey (ORCID: https://orcid.org/0000-0002-9659-7096)
- Patricia P. Chang
Institutions
- University of North Carolina at Chapel Hill (US)
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- Cleveland Clinic (US)
- Johns Hopkins University (US)
- Duke University (US)
- University of Washington (US)
- Jackson Memorial Hospital (US)
- University of Mississippi Medical Center (US)
- NYU Langone Health (US)
- National Heart, Lung, and Blood Institute (US)
- National Institute on Aging (US)
- Penn State Milton S. Hershey Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
- Stanford University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-08-21
- DOI
- https://doi.org/10.1126/sciadv.aec5063
- Primary Topic
- Health, Environment, Cognitive Aging
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health