JAMA Netw Open. 2025 May 1;8(5):e2510016. doi: 10.1001/jamanetworkopen.2025.10016.
ABSTRACT
IMPORTANCE: Although structural and social determinants of health (SSDH) have been consistently associated with health disparities, percentage African genetic ancestry (AGA) has been suggested as a risk factor associated with common diseases in Black populations. Appropriate use and interpretation of percentage AGA in understanding health disparities has been complicated by the fact that percentage AGA is correlated with genetic and nongenetic factors.
OBJECTIVE: To evaluate associations of SSDH with mortality in the context of percentage AGA and how percentage AGA is correlated with SSDH.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study investigated data from the Multiethnic Cohort (MEC) Study, in which participants were enrolled from 1993 through 1996 and followed up until death or censoring on December 31, 2019. Participant data were analyzed between March and June 2023. The population-based sample was predominantly from Los Angeles County, California, consisting of self-identified Black adults aged 45 to 75 years who enrolled into the MEC Study; completed a baseline demographic, clinical, and lifestyle questionnaire; and provided biospecimens.
EXPOSURES: The Index of Concentration at the Extremes (ICE), capturing social polarization based on income and racial composition, and a neighborhood socioeconomic status (NSES) index were computed from the 1990 Census, scaled to county-specific quintiles, and linked to residential census tracts at study enrollment. Percentage AGA was estimated using 21 431 single-nucleotide variations based on similarity with African continental referent data.
MAIN OUTCOMES AND MEASURES: Multivariable hazard ratios (HRs) for all-cause mortality were estimated from Cox models. Correlation of percentage AGA with SSDH measures was described.
RESULTS: After exclusions, 9685 participants were included (mean [SD] age, 61.0 [8.9] years; 5593 female [57.7%]), with a mean (SD) percentage AGA of 75.0% (14.0%). There were 5504 deaths over 204 463 person-years of follow-up. Comparing the most with least advantaged quintile, income ICE (adjusted HR [aHR], 1.30; 95% CI, 1.16-1.45) and NSES (aHR, 1.37, 95% CI, 1.20-1.56) were associated with lower all-cause mortality. Minimal changes were observed after adjusting for percentage AGA; for example, comparing the most with least advantaged quintile, NSES (aHR, 1.36; 95% CI, 1.19-1.55) remained associated with lower all-cause mortality. There was no association between percentage AGA and mortality after adjustment (aHR per 10-percentage point change in percentage AGA, 1.01; 95% CI, 0.99-1.03).
CONCLUSIONS AND RELEVANCE: In this study, associations of SSDH with mortality persisted with adjustment for percentage AGA. Findings support the hypothesis that SSDH should be the primary factors to consider for eliminating health disparities.
PMID:40358946 | DOI:10.1001/jamanetworkopen.2025.10016
