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Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts

  • METABOLOMIC EPIDEMIOLOGY
  • Published:
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Abstract

There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities. We therefore aimed to estimate metabolomic differences between Black and White women in the U.S. We leveraged data from two prospective cohorts: the Nurses’ Health Study (NHS; n = 2077) and Women’s Health Initiative (WHI; n = 2128). The WHI served as the replication cohort. Plasma metabolites (n = 334) were measured via liquid chromatography-tandem mass spectrometry. Observed metabolomic differences were estimated using linear regression and metabolite set enrichment analyses. Residual metabolomic differences in a hypothetical population in which the distributions of 14 risk factors were equalized across racial groups were estimated using inverse odds ratio weighting. In the NHS, Black-White differences were observed for most metabolites (75 metabolites with observed differences \(\ge \)|0.50| standard deviations). Black women had lower average levels than White women for most metabolites (e.g., for N6, N6-dimethlylysine, mean Black-White difference = − 0.98 standard deviations; 95% CI: − 1.11, − 0.84). In metabolite set enrichment analyses, Black women had lower levels of triglycerides, phosphatidylcholines, lysophosphatidylethanolamines, phosphatidylethanolamines, and organoheterocyclic compounds, but higher levels of phosphatidylethanolamine plasmalogens, phosphatidylcholine plasmalogens, cholesteryl esters, and carnitines. In a hypothetical population in which distributions of 14 risk factors were equalized, Black-White metabolomic differences persisted. Most results replicated in the WHI (88% of 272 metabolites available for replication). Substantial differences in metabolomic profiles exist between Black and White women. Future studies should prioritize racial representation.

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Data availability

Due to participant confidentiality and privacy concerns, requests to access the NHS and WHI data must be submitted in writing and must comply with the data request procedures of the NHS and WHI. Investigators wishing to use NHS data are asked to submit a brief description of the proposed project. Go to https://www.nurseshealthstudy.org/researchers (contact email: nhsaccess@channing.harvard.edu) for more details on accessing the NHS data. To request use of the WHI data, go to https://www.whi.org/get-started. Statistical code used in this manuscript is publicly available via GitHub: https://github.com/emma-mcgee/racial-differences-in-metabolomic-profiles

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Funding

The Nurses’ Health Study analyses were funded by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (grants UM1 CA186107, R01 CA49449, and P01 CA87969). Census tract variables were ascertained through funding from the National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services (grants R01 ES017017 and R01 ES028033). The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. Metabolomic analysis in the Women’s Health Initiative was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contract HHSN268201300008C. A list of WHI investigators is available online at https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. E.E. McGee was supported by funding from the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard. The funders had no role in the design of the study; collection, analysis, or interpretation of data; writing of the report; or decision to submit the manuscript for publication. The content presented here is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or any other sponsors.

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Authors and Affiliations

  1. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Emma E. McGee, Oana A. Zeleznik, Bernard A. Rosner, Walter C. Willett & A. Heather Eliassen

  2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Emma E. McGee, Walter C. Willett & A. Heather Eliassen

  3. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA

    Emma E. McGee, Clary B. Clish & Julian Avila-Pacheco

  4. Division of Women’s Health, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Raji Balasubramanian, Jie Hu & Kathryn M. Rexrode

  5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Bernard A. Rosner

  6. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA

    Jean Wactawski-Wende

  7. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Walter C. Willett & A. Heather Eliassen

  8. Department of Population Health Sciences, Weill Cornell Medical College, New York, USA

    Rulla M. Tamimi

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  1. Emma E. McGee
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  2. Oana A. Zeleznik
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  3. Raji Balasubramanian
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  4. Jie Hu
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  6. Jean Wactawski-Wende
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  9. Walter C. Willett
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  10. Kathryn M. Rexrode
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  12. A. Heather Eliassen
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Conceptualization and design of the study: EEM, OAZ, CBC, WCW, KMR, RMT, and AHE. Acquisition of data: CBC, JAP, WCW, KMR, RMT, and AHE. Analysis of data: EEM. Interpretation of data: EEM, OAZ, RB, JH, BAR, JWW, CBC, JAP, WCW, KMR, RMT, and AHE. Drafting of manuscript: EEM. Review and approval of final manuscript: EEM, OAZ, RB, JH, BAR, JWW, CBC, JAP, WCW, KMR, RMT, and AHE. EEM had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Emma E. McGee.

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The authors have no relevant financial or non-financial interest to disclose.

Ethics approval

The NHS study protocol was approved by the institutional review boards of Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health. Institutional review board approval for the WHI was obtained at each clinical center.

Consent to participate

In the NHS, return of the completed questionnaire was considered to imply informed consent. In the WHI, informed consent was obtained from all participants.

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McGee, E.E., Zeleznik, O.A., Balasubramanian, R. et al. Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts. Eur J Epidemiol (2024). https://doi.org/10.1007/s10654-024-01111-x

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