Race/Ethnicity/Ancestry (REA) and Disease: A Complex Interplay of Social and Biological Factors

Michel Tibayrenc

doi:10.53941/dbgs.2026.100001

Abstract

The connection between human genetic and geographical diversity on one hand, and disease distribution on the other hand, has been a subject of ongoing research. A key challenge lies in defining the relevant units of analysis (RUAs) within human populations to accurately assess the impact of disease. While “race” is often considered a social construct, biomedical studies frequently utilize major geographical populations—European, Asian, and African groups—As RUAs. Other groups like “Hispanics” or Native Americans are also commonly used. This review examines the findings of this prevalent approach and argues that it offers significant advantages over the historically dominant model that focused solely on European populations.

References

1.
Abdellaoui, A.; Yengo, L.; Verweij, K.J.H.; et al. 15 years of GWAS discovery: Realizing the promise. Am. J. Hum. Genet. 2023, 110, 179–194.
2.
Alexandre, L. ChatGPT va Nous Rendre Immortels; JCLattès: Paris, France, 2024.
3.
Arama, C.; Maiga, B.; Dolo, A.; et al. Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa? Acta Trop. 2015, 146, 152–156.
4.
Armengol, L.; Villatoro, S.; González, J.R.; et al. Identification of Copy Number Variants Defining Genomic Differences among Major Human Groups. PLoS ONE 2009, 4, e7230. https://doi.org/10.1371/journal.pone.0007230.
5.
Avise, J.C. Molecular Markers, Natural History and Evolution, 2nd ed.; Chapman & Hall: London, UK.
6.
Barbujani, G.; Colonna, V. Human genome diversity: Frequently asked question. Trends Genet. 2010, 26, 285–295.
7.
Bick, A.G.; The All of Us Research Program Genomics Investigators. Genomic data in the All of Us Research Program. Nature 2024, 627, 340–346. https://doi.org/10.1038/s41586-023-06957-x.
8.
Boahen, C.K.; Temba, G.S.; Kullaya, V.I.; et al. A functional genomics approach in Tanzanian population identifies distinct genetic regulators of cytokine production compared to European population. Am. J. Hum. Genet. 2022, 109, 471–485.
9.
Brothers, K.B.; Bennett, R.L.; Cho, M.K. Taking an antiracist posture in scientific publications in human genetics and genomics. Genet. Med. 2021, 23, 1004–1007. https://doi.org/10.1038/s41436-021-01109-w.
10.
Bucheton, B.; Kheir, M.M.; El-Safi, S.H.; et al. The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan. Microbes Infect. 2002, 4, 1449–1457.
11.
Budowle, B.; Sajantila, A. Short tandem repeats—How microsatellites became the currency of forensic genetics. Nat. Rev. Genet. 2024, 25, 450.
12.
Byappanahalli, A.M.; Omoniyi, V.; Hooten, N.N.; et al. Extracellular vesicle mitochondrial DNA levels are associated with race and mitochondrial DNA haplogroup. iScience 2024, 27, 108724.
13.
Chapman, S.J.; Hill, A.V.S. Human genetic susceptibility to infectious disease. Nat. Rev. Genet. 2012, 13, 175–188.
14.
Choudhury, A.R.; Singh, K.K. Mitochondrial Determinants of Cancer Health Disparities. In Seminars in Cancer Biology; Academic Press: New York, NY, USA, 2017; Volume 47, pp. 125–146.
15.
Cochran, G.; Harpending, H. The 10,000 Year Explosion—How Civilization Accelerated Human Evolution. In Basic Books; A Member of the Perseus Books Group: New York, NY, USA, 2009.
16.
Corona, E.; Chen, R.; Sikora, M.; et al. Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration. PLoS Genet. 2013, 9, e1003447. https://doi.org10.1371/journal.pgen.1003447.
17.
Dean, M.; Carrington, M.; Winkler, C.; et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 1996, 273, 1856–1862.
18.
Duncan, R.G.; Krishnamoorthy, R.; Harms, U.; et al. The sociopolitical in human genetics education. Science 2024, 383, 826–828.
19.
Fu, W.; O’connor, T.D.; Jun, G.; et al. Analysis of 6515 exomes reveals the recent origin of most human protein-coding variants. Nature 2013, 493, 216–220.
20.
Gentillini, M.; Duflo, B.; Danis, M.; et al. Médecine Tropicale, 4th éd.; Médecine-Sciences, Flammarion: Paris, France, 1986.
21.
Gonzaga-Jauregui, C.; Lupski, J.R.; Gibbs, R.A. Human Genome Sequencing in Health and Disease. Annu. Rev. Med. 2012, 63, 35–61.
22.
Burchard, E.G.; Ziv, E.; Coyle, N.; et al. The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice. New Engl. J. Med. 2003, 348, 1170–1175.
23.
Graves, J.L.; Goodman, A.H. Racism, not Race; Answers to Frequently Asked Questions; Columbia University Press: New York, NY, USA, 2022.
24.
Guha, S.; Rosenfeld, J.A.; Malhotra, A.K.; et al. Implications for health and disease in the genetic signature of the Ashkenazi Jewish population. Genome Biol. 2012, 13, R2. https://doi.org10.1186/gb-2012-13-1-r2.
25.
Gurdasani, D.; Carstensen, T.; Tekola-Ayele, F.; et al. The African Genome Variation Project shapes medical genetics in Africa. Nature 2015, 517, 327–332.
26.
Hardelid, P.; Cortina-Borja, M.; Munro, A.; et al. The Birth Prevalence of PKU in Populations of European, South Asian and Sub-Saharan African Ancestry Living in South East England. Ann. Hum. Genet. 2008, 72, 65–71.
27.
Harris, K. Evidence for recent, population-specific evolution of the human mutation rate. Proc. Nat. Acad. Sci. USA 2015, 112, 3439–3444.
28.
Hindorff, L.A.; Bonham, V.L.; Brody, L.C.; et al. Prioritizing diversity in human genomics research. Nat. Rev. Genet. 2018, 19, 175–185.
29.
Hoffmann, T.J.; Graff, R.E.; Madduri, R.K.; et al. Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups. Nat. Genet. 2025, 57, 334–344. https://doi.org/10.1038/s41588-024-02068-z.
30.
Jaratlerdsiri, W.; Jiang, J.; Gong, T.; et al. African-specific molecular taxonomy of prostate cancer. Nature 2022, 609, 552–559.
31.
Jia, G.; Ping, J.; Guo, X.; et al. Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction. Nat. Genet. 2024, 56, 819–826.
32.
Jordan, B. L’humanité au Pluriel La Génétique et la Question des Races; Éditions du Seuil: Paris, France, 2008.
33.
Jorde, L.B.; Wooding, S.P. Genetic variation, classification and ‘race’. Nat. Genet. 2004, 11, S28–S33.
34.
Karlsson, E.K.; Kwiatkowski, D.P.; Sabeti, P.C. Natural selection and infectious disease in human populations. Nat. Rev. Genet. 2014, 15, 379–383.
35.
Koch, L. Impact of genetic ancestry on viral infection response. Nat. Rev. Genet. 2022, 23, 72. https://doi.org/10.1038/s41576-021-00442-9.
36.
Lewontin, R.C. The apportionment of human diversity. Evol. Biol. 1972, 6, 381–398.
37.
Karlsson, E.K.; Kwiatkowski, D.P.; Sabeti, P.C. Association between mitochondrial genetic variation and breast cancer risk: The Multiethnic Cohort. PLoS ONE 2019, 14, e0222284. https://doi.org/10.1371/journal.pone.0222284.
38.
Maglo, K.N.; Mersha, T.B.; Martin, L.J. Population Genomics and the Statistical Values of Race: An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research. Front. Genet. 2016, 7, 22. https://doi.org/10.3389/fgene.2016.00022.
39.
Manry, J.; Quintana-Murci, L. A Genome-Wide Perspective of Human Diversity and Its Implications in Infectious Disease. Cold Spring Harb. Perspect. Med. 2013, 3, a012450.
40.
Martin, A.R.; Gignoux, C.R.; Walters, R.K.; et al. Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations. Am. J. Hum. Genet. 2017, 100, 635–649.
41.
Marouli, E.; Graff, M.; Medina-Gomez, C.; et al. Rare and low-frequency coding variants alter human adult height. Nature 2017, 542, 186–193.
42.
Martini, R.; Davis, M.B. The DARC side of genetics in cancer: Breast cancer disparities. Am. J. Hum. Genet. 2024, 111, 1261–1264.
43.
McLaren, P.J.; Porreca, I.; Iaconis, G.; et al. Africa-specific human genetic variation near CHD1L associates with HIV-1 load. Nature 2023, 620, 1025–1030.
44.
Mersha, T.B.; Abebe, T. Self-reported race/ethnicity in the age of genomic research: Its potential impact on understanding health disparities. Hum. Genom. 2015, 9, 1. https://doi.org/10.1186/s40246-014-0023-x.
45.
Moreno-Estrada, A.; Gignoux, C.R.; Fernández-López, J.C.; et al. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 2014, 344, 1280–1285.
46.
Mountain, J.L.; Risch, N. Assessing genetic contribution to phenotypic differences among “racial” and “ethnic” groups. Nat. Genet. 2004, 36, S48–S53.
47.
Neel, J.V. Diabetes Mellitus: A ‘Thrifty’ Genotype Rendered Detrimental by ‘Progress’? Am. J. Hum. Genet. 1962, 14, 353–362.
48.
Nei, M. The theory of genetic distance and evolution of human races. JPN. J. Hum. Genet. 1978, 23, 341–369.
49.
Nelson, M.R.; Wegmann, D.; Ehm, M.G.; et al. An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People. Science 2012, 337, 100–104.
50.
Nichols, R. Gene trees and species trees are not the same. Trends Ecol. Evol. 2001, 16, 358–364.
51.
Niedzwiedz, C.L.; O’Donnell, C.A.; Jani, B.D.; et al. Ethnic and socioeconomic differences in SARS-CoV-2 infection: Prospective cohort study using UK Biobank. BMC Med. 2020, 18, 160.
52.
Omiye, J.A.; Lester, J.C.; Spichak, S.; et al. Large language models propagate race-based medicine. NPJ Digit. Med.2023, 6, 195. https://doi.org/10.1038/s41746-023-00939-z.
53.
Ostrer, H.; Skorecki, K. The population genetics of the Jewish people. Hum. Genet. 2013, 132, 119–127.
54.
Parens, E. The Inflated Promise of Genomic Medicine. Available online: https://www.scientificamerican.com/blog/observations/the-inflated-promise-of-genomic-medicine/ (access on 10 July 2025).
55.
Pfaff, C.L.; Parra, E.J.; Bonilla, C.; et al. Population Structure in Admixed Populations: Effect of Admixture Dynamics on the Pattern of Linkage Disequilibrium. Amer. J. Hum. Genet. 2001, 68, 198–207.
56.
Quintana-Murci, L. Le Peuple des Humains; Odile Jacob: Paris, France, 2021.
57.
Reardon, S. Alzheimer’s drug trials plagued by lack of racial diversity. Nature 2023, 620, 256–257.
58.
Reid, D.M.; Barber, R.C.; Thorpe, R.J.; et al. Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer’s disease. NPJ Aging 2022, 8, 2. https://doi.org/10.1038/s41514-022-00082-1.
59.
Risch, N.; Burchard, E.; Ziv, E.; et al. Categorization of humans in biomedical research: Genes, race and disease. Genome Biol. 2002, 3. https://doi.org/10.1186/gb-2002-3-7-comment2007.
60.
Roberts, D.E. The art of medicine. Abolish race correction. Lancet 2021, 397, 17–18.
61.
Shelton, J.F.; Shastri, A.J.; Ye, C.; et al. Trans-ancestry analysis reveals genetic and nongenetic associations with COVID-19 susceptibility and severity. Nat. Genet. 2021, 53, 801–808.
62.
Shi, Y.; Niu, Y.; Zhang, P.; et al. Characterization of genome-wide STR variation in 6487 human genomes. Nat. Commun. 2023, 14, 2092. https://doi.org/10.1038/s41467-023-37690-8.
63.
Shukla, P.; Singh, K.K. Uncovering Mitochondrial Determinants of Racial Disparities in Ovarian Cancer. Trends Cancer 2021, 7, 93–97.
64.
Sudmant, P.H.; Rausch, T.; Gardner, E.J.; et al. An integrated map of structural variation in 2504 human genomes. Nature 2015, 526, 75–81.
65.
Tennessen, J.A.; Bigham, A.W.; O’connor, T.D.; et al. Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes. Science 2012, 337, 64–69.
66.
The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 2015, 526, 68–74.
67.
Tibayrenc, M. The Impact of Human Genetic Diversity in the Transmission and Severity of Infectious Diseases. In Infectious Disease: Host-Pathogen Evolution, Dronamraju, K., Ed.; Cambridge University Press: Cambridge, UK, 2004; pp. 315–324.
68.
Tibayrenc, M. The Race/Ethnic Debate: An Outsider’s View. In On Human Nature: Biology, Psychology, Ethics, Politics, and Religion; Tibayrenc, M., Ayala, F.J., Eds.; Elsevier/Academic Press: San Diego, CA, USA, 2017.
69.
Tishkoff, S.A.; Kidd, K.K. Implications of biogeography of human populations for “race” and medicine. Nat. Genet. 2004, 36, S21–S27.
70.
Vallois, H.V. Les Races Humaines; Presses Universitaires de France: Paris, France, 1976.
71.
Van Valen, L. A New Evolutionary Law (1973). In Foundations of Macroecology; University of Chicago Press: Chicago, IL, USA, 2014; pp. 284–314.
72.
Vasseur, E.; Quintana-Murci, L. The impact of natural selection on health and disease: Uses of the population genetics approach in humans. Evol. Appl. 2013, 6, 596–607.
73.
Verma, A.; Huffman, J.E.; Rodriguez, A.; et al. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science 2024, 385, eadj1182.
74.
Wang, Y.; He, Y.; Shi, Y.; et al. Aspiring toward equitable benefits from genomic advances to individuals of ancestrally diverse backgrounds. Am. J. Hum. Genet. 2024, 111, 809–824.
75.
Winther, R.G. A Beginner’s Guide to the New Population Genomics of Homo sapiens: Origins, Race, and Medicine. Harv. Rev. Philos. 2018, XXV, 1–18.
76.
Wright, S. The genetical structure of populations. Ann. Eugen. 1951, 15, 323–354.
77.
Xie, N. Building a catalogue of short tandem repeats in diverse populations. Nat. Rev. Genet. 2024, 25, 457.
78.
Yudell, M.; Roberts, D.; DeSalle, R.; et al. NIH must confront the use of race in science. Science 2020, 369, 1313–1314.

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