Objective The goal of this study was to investigate the association of perceived discrimination with health outcomes and disparities. Materials and Methods The study cohort consists of 60,180 participants from the four largest SIRE groups in the All of Us Research Program participant body: Asian (1,291), Black (4,726), Hispanic (5,336), and White (48,827). A perceived discrimination index (PDI) was derived from participant responses to the Social Determinants of Health survey, and the All of Us Researcher Workbench was used to analyze associations and mediation effects of PDI and self-identified race and ethnicity (SIRE) with 1,755 diseases. Results The Black SIRE group has the greatest median PDI, followed by the Asian, Hispanic, and White groups. The Black SIRE group shows the greatest number of diseases with elevated risk relative to the White reference group, followed by the Hispanic and Asian groups. PDI was found to be positively and significantly associated with 489 out of 1,755 (27.86%) diseases. Mental Disorders is the disease category with the greatest proportion of diseases positively and significantly associated with PDI: 59 out of 72 (81.94%) diseases. Mediation analysis showed that PDI mediates 69 out of 351 (19.66%) Black-White disease disparities. Discussion Perceived discrimination is significantly associated with risk for numerous diseases and mediates Black-White disease disparities in the All of Us participant cohort. Conclusion This work highlights the role of discrimination as an important social determinant of health and provides a means by which it can be quantified and modeled on the All of Us platform.

The authors have declared no competing interest.

VL, SG, and LMR were supported by the Division of Intramural Research (DIR) of the National Institute on Minority Health and Health Disparities (NIMHD) at NIH, (Award Number: 1ZIAMD000018). LMR was supported by the National Institutes of Health (NIH) Distinguished Scholars Program (DSP). IKJ was supported by the by the IHRC-Georgia Tech Applied Bioinformatics Laboratory (Award Number: RF383).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The All of Us operational protocol (#2016-05) is approved by the NIH Institutional Review Board. Written informed consent was obtained from all participants. All data available to researchers has had direct identifiers removed and has been further modified to minimize re-identification risks. Because the All of Us data were not collected specifically for this study and no one on the study team has access to the subject identifiers linked to the data, this study is not considered human subjects research according to the NIH Revised Common Rule for the Protection of Human Subjects: https://grants.nih.gov/policy/humansubjects/hs-decision.htm.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All code and data used in this study are made available on the All of Us Researcher Workbench.