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

Emma E McGee; Oana A Zeleznik; Raji Balasubramanian; Jie Hu; Bernard A Rosner; Jean Wactawski-Wende; Clary B Clish; Julian Avila-Pacheco; Walter C Willett; Kathryn M Rexrode; Rulla M Tamimi; A Heather Eliassen

doi:10.1007/s10654-024-01111-x

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

Eur J Epidemiol. 2024 May 4. doi: 10.1007/s10654-024-01111-x. Online ahead of print.

Authors

Emma E McGee^{1

2

3}, Oana A Zeleznik⁴, Raji Balasubramanian⁵, Jie Hu⁵, Bernard A Rosner^{4

6}, Jean Wactawski-Wende⁷, Clary B Clish⁸, Julian Avila-Pacheco⁸, Walter C Willett^{4

9

10}, Kathryn M Rexrode⁵, Rulla M Tamimi¹¹, A Heather Eliassen^{4

9

10}

Affiliations

¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. emcgee@hsph.harvard.edu.
² Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. emcgee@hsph.harvard.edu.
³ Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. emcgee@hsph.harvard.edu.
⁴ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Division of Women's Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
⁸ Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
⁹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
¹⁰ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Department of Population Health Sciences, Weill Cornell Medical College, New York, USA.

PMID: 38703248
DOI: 10.1007/s10654-024-01111-x

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 $\geq$ |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.

Keywords: Counterfactual analysis; Health disparities; Metabolomics; Race; Racial differences.

Abstract

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