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Deconstructing the relationship between genetics and race

Nature Reviews Genetics volume 5, pages 598609 (2004) | Download Citation



The success of many strategies for finding genetic variants that underlie complex traits depends on how genetic variation is distributed among human populations. This realization has intensified the investigation of genetic differences among groups, which are often defined by commonly used racial labels. Some scientists argue that race is an adequate proxy of ancestry, whereas others claim that race belies how genetic variation is apportioned. Resolving this controversy depends on understanding the complicated relationship between race, ancestry and the demographic history of humans. Recent discoveries are helping us to deconstruct this relationship, and provide better guidance to scientists and policy makers.

Key points

  • Highlighting genetic differences among people could unfortunately reinforce stereotypical features of populations, but exploring the genetic influence on common health-related traits and disparities could also be beneficial to human health.

  • Accurate inference of an individual's ancestry using genetic data depends on several factors, including the number of genotypes used, the degree of differentiation among groups and how each group is sampled.

  • Inferences of human population structure based on genetic data often differ from inferences based on phenotypic characteristics.

  • Although there might be little variation among groups, it is highly structured and therefore useful for distinguishing groups and allocating individuals into groups.

  • Insofar as geographical ancestry corresponds to some notions of race, patterns of genetic variation will also co-vary with these notions.

  • The inaccurate measure of ancestry afforded by proxies of genetic relationships such as race or ethnicity can sometimes be useful, but in other circumstances, might lower the chances of findings disease-susceptibility loci and lessen the predictive value of clinical inferences.

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  1. 1.

    Genetics and the biology of race crossing. Science 182, 790–796 (1973).

  2. 2.

    The Mismeasure of Man (W. W. Norton Press, New York, 1981).

  3. 3.

    Human Diversity (Scientific American Books, Inc., New York, 1982).

  4. 4.

    & Does Race Exist? Sci. Am. 289, 78–85 (2003).

  5. 5.

    Race in North America: Origin and Evolution of a Worldview, 2nd edn (Westview Press, Boulder, 1999).

  6. 6.

    , , & Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genet. 33, 177–182 (2003).

  7. 7.

    & Identity and genetic ancestry gracing. B. Med. J. 325, 1469–1471 (2002).

  8. 8.

    & Race, ethnicity, and genomics: social classifications as proxies of biological heterogeneity. Genome Res. 12, 844–850 (2002). An introduction to some of the problems and challenges of trying to understand the relationship between the social definitions of populations and biologically defined groups.

  9. 9.

    & Low nucleotide diversity in man. Genetics 129, 513–523 (1991).

  10. 10.

    & Genetic perspectives on human origins and differentiation. Annu. Rev. Genom. Hum. Genet. 1, 361–385 (2000). A good review of genetic evidence on the evolution of modern humans as it pertains to some of the fundamental questions about human demographic history and the impact of natural selection.

  11. 11.

    , , & Evidence for a complex demographic history of chimpanzees. Mol. Biol. Evol. 5, 799–808 (2004).

  12. 12.

    , & Testing the neutral theory of molecular evolution with genomic data from Drosophila. Nature 415, 1024–1026 (2002).

  13. 13.

    & Genic variation within and between the three major races of man, Caucasoids, Negroids, and Mongoloids. Am. J. Hum. Genet. 26, 421–443 (1974).

  14. 14.

    & Multilocus genotypes, a tree of individuals, and human evolutionary history. Am. J. Hum. Genet. 61, 705–718 (1997).

  15. 15.

    et al. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. Proc. Natl Acad. Sci. USA 88, 839–843 (1991).

  16. 16.

    et al. The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data. Am. J. Hum. Genet. 66, 979–988 (2000).

  17. 17.

    et al. The genomic distribution of population substructure in four popoulations using 8,255 autosomal SNPs. Hum. Genomics (in the press).

  18. 18.

    et al. Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms. Genome Res. 13, 1607–1618 (2003).

  19. 19.

    et al. Population genetic structure of variable drug response. Nature Genet. 29, 265–269 (2001).

  20. 20.

    & Number of SNPS loci needed to detect population structure. Hum. Hered. 55, 37–45 (2003).

  21. 21.

    , , & Robustness of the inference of human population structure: a comparison of X-chromosomal and autosomal microsatellites. Hum. Genom. 1, 87–97 (2004).

  22. 22.

    , , & Informativeness of genetic markers for inference of ancestry. Am. J. Hum. Genet. 73, 1402–1422 (2003). A comprehensive analysis of worldwide human microsatellite data that examines the amount of information that multi-allelic markers provide about individual ancestry.

  23. 23.

    & Race, ancestry, and genes: implications for defining disease risk. Annu. Rev. Genom. 4, 33–67 (2003).

  24. 24.

    et al. Human population genetic structure and inference of group membership. Am. J. Hum. Genet. 72, 578–589 (2003).

  25. 25.

    et al. Genetic structure of human populations. Science 298, 2381–2385 (2002). A comprehensive analysis of global patterns of human population structure. Its shows that although there is substantial geographical structuring among populations, the proportion of ancestry of many individuals from one or more of these populations is highly variable.

  26. 26.

    et al. Genetic evidence on the origins of Indian caste populations. Genome Res. 11, 994–1004 (2001).

  27. 27.

    & Patterns of human genetic diversity: implications for human evolutionary history and disease. Annu. Rev. Genom. Hum. Genet. 4, 293–340 (2003).

  28. 28.

    & in Human Population Genetics (ed. Majumder, P. P.) 207–232 (Plenum Press, New York, 1993).

  29. 29.

    et al. Genetic origins of the Ainu inferred from combined DNA analyses of maternal and paternal lineages. J. Hum. Genet. 49, 187–193 (2004).

  30. 30.

    & Comparison of genetic differentiation at marker loci and quantitative traits. J. Evol. Biol. 14, 892–903 (2001).

  31. 31.

    & Genetic analysis of African populations: human evolution and complex disease. Nature Rev. Genet. 3, 611–621 (2002).

  32. 32.

    et al. Emergence of FY*Anull in a Plasmodium vivax-endemic region of Papua New Guinea. Proc. Natl Acad. Sci. USA. 96, 13973–13977 (1999).

  33. 33.

    et al. A strong signature of balancing selection in the 5′ cis-regulatory region of CCR5. Proc. Natl Acad. Sci. USA 99, 10539–10544 (2002).

  34. 34.

    et al. Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am. J. Hum. Genet. 74, 637–646 (2004).

  35. 35.

    & FDA races in wrong direction. Science 301, 466 (2003).

  36. 36.

    The apportionment of human diversity. Evol. Biol. 6, 381–398 (1972).

  37. 37.

    & Analysis of evolution: evolutionary rates, independence, and treeness. Theor. Pop. Biol. 8, 127–165 (1975).

  38. 38.

    , & Human population genomics: a bridge from evolutionary history to genetic medicine. Hum. Mol. Genet. 10, 2199–2207 (2001).

  39. 39.

    The genetical structure of populations. Annu. Eugenics 15, 323–354 (1951).

  40. 40.

    & Estimating F-statistics. Annu. Rev. Genom. Hum. Genet. 36, 721–750 (2002).

  41. 41.

    , , , & Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 12, 1805–1814 (2002).

  42. 42.

    & Human genetic diversity and the nonexistence of biological races. Hum. Biol. 75, 449–471 (2003).

  43. 43.

    Human races: a genetic and evolutionary perspective. Am. Anthropol. 100, 632–650 (1999).

  44. 44.

    Genetic 'differences.' Genomics 79, 145 (2002).

  45. 45.

    AAA. American Anthropological Association Statement on Race. Am. Anthropol. 100, 712–713 (1999).

  46. 46.

    Office of Management and Budget. Revisions to the standards for the classification of federal data on race and ethnicity [online], <> (1997).

  47. 47.

    Human genetic diversity: Lewontin's fallacy. BioEssays 25, 798–801 (2003).

  48. 48.

    & Mapping human history. Science 298, 2342–2343 (2002).

  49. 49.

    & On the allelic spectrum of human disease. Trends Genet. 17, 199–204 (2001).

  50. 50.

    et al. The structure of haplotype blocks in the human genome. Science 296, 22225–2229 (2002).

  51. 51.

    Population genetic analysis of ascertained SNP data. Hum. Genom. 1, 218–224 (2004).

  52. 52.

    et al. Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans. Nature Genet. 33, 518–521 (2003).

  53. 53.

    et al. Haplotype diversity across 100 candidate genes for inflammation, lipid metabolism, and blood pressure regulation in two populations. Am. J. Hum. Genet. 74, 610–622 (2004).

  54. 54.

    et al. Skin pigmentation, biogeographical ancestry, and admixture mapping. Hum. Genet. 112, 387–399 (2003). A clear example of how estimates of individual ancestry proportions can be used to identify genotypes that influence phenotypes that differ between populations.

  55. 55.

    et al. Control of confounding in genetic associations in stratified populations. Am. J. Hum. Genet. 72, 1492–1504 (2003).

  56. 56.

    & Use of unlinked genetic markers to detect population structure using multilocus genotype data. Genetics 155, 945–959 (1999).

  57. 57.

    et al. Matching strategies for genetic association studies in structured populations. Am. J. Hum. Genet. 74, 317–325 (2004).

  58. 58.

    et al. Estimating African–American admixture proportions by use of population-specific alleles. Am. J. Hum. Genet. 63, 1839–1851 (1998).

  59. 59.

    et al. A classifier for the SNP-based inference of ancestry. J. Forens. Sci. 48, 1–12 (2003).

  60. 60.

    & Genetic ancestry and the search for personalized genetic histories. Nature Rev. Genet. 5, 611–618 (2004).

  61. 61.

    & Signatures of natural selection in the human genome. Nature Rev. Genet. 4, 99–111 (2003).

  62. 62.

    , , , & Global distribution of the CCR5 gene 32-basepair deletion. Nature Genet. 16, 100–103 (1997).

  63. 63.

    , & Ethnic differences and disease phenotypes. Science 300, 739–740 (2003).

  64. 64.

    Impact of race/ethnicity on molecular pathways in human cancer. Nature Rev. Cancer 4, 79–84 (2003).

  65. 65.

    Race and medicine. Science 302, 594–596 (2003).

  66. 66.

    Does race matter in heart failure. Am. Heart J. 146, 203–206 (2003).

  67. 67.

    et al. Association of African genetic admixture with resting metabolic rate and obesity among women. Obes. Res. 11, 904–911 (2003).

  68. 68.

    et al. Using genetic admixture to explain racial differences in insulin-related phenotypes. Diabetes 52, 1047–1051 (2003).

  69. 69.

    et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278, 1349–1356 (1997).

  70. 70.

    et al. Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science 282, 1907–1911 (1998).

  71. 71.

    et al. Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes. Proc. Natl Acad. Sci. USA. 96, 12004–12009 (1999). A noteworthy example of genetic variants associated with different outcomes of HIV-1 infection in African–Americans versus European–Americans.

  72. 72.

    et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606 (2001).

  73. 73.

    et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001).

  74. 74.

    Lack of common NOD2 variants in Japanese patients with Crohn's disease. Gastroenterology 123, 86–91 (2002).

  75. 75.

    Beyond consent: ethical and social issues in genetic testing. Nature Rev. Genet. 2, 147–151 (2001).

  76. 76.

    & Use of race and ethnicity in biomedical publication. JAMA 289, 2709–2716 (2003).

  77. 77.

    & Toward a new vocabulary of human genetic variation. Science 298, 1337–1338 (2003).

  78. 78.

    & Race, the reality of human differences. (Westview, Boulder, Colorado, 2004).

  79. 79.

    'Race' and the construction of human identity. Am. Anthropol. 100, 690–702 (1999).

  80. 80.

    , , & Categorization of humans in biomedical research: genes, race, and disease. Genome Biol. 3, 1–12 (2003).

  81. 81.

    et al. The importance of race and ethnic background in biomedical research and clinical practice. N. Engl. J. Med. 348, 1170–1175 (2003).

  82. 82.

    , & Race and genomics. N. Engl. J. Med. 348, 1166–1170 (2003).

  83. 83.

    Racial profiling in medical research. N. Engl. J. Med. 344, 1392–1393 (2001).

  84. 84.

    Racial meanings and scientific methods: changing policies for NIH-sponsored publications reporting human variation. J. Health Politics 6, 1033–1087 (2003).

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We thank S. Guthery and M. Pungliya for technical assistance, T. Frudakis for access to data from DNAPrint Genomics, S. Olson and L. Jorde for discussion, and four anonymous reviewers for comments and criticisms. M.B. and S.W. are supported by the US National Institutes of Health and the National Science Foundation.

Author information


  1. Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA.

    • Michael Bamshad
    •  & Stephen Wooding
  2. Department of Pediatrics, University of Utah, Salt Lake City, Utah 84112, USA.

    • Michael Bamshad
  3. Genaissance Pharmaceuticals, New Haven, Connecticut, 06511, USA.

    • Benjamin A. Salisbury
    •  & J. Claiborne Stephens


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Competing interests

Benjamin A. Salisbury and J. Claiborne Stephens are both employees and shareholders of Genaissance Pharmaceuticals, Inc.

Corresponding author

Correspondence to Michael Bamshad.

Supplementary information

Text files

  1. 1.

    supplementary information S1 (data)100 Alu insertion polymorphisms in Africans, Asians and EuropeansFile name: Bamshad_continental_alu_100.txt Refers to figures: 1a,1b,3a Column 1: Af, African; Eu, European; As, Asian. Column 2: continent code. Columns 3–103: Alu genotypes: 0, absent; 1, present. The genotype of each individual occupies 2 lines of text. Missing data indicated by ‘-9’.

  2. 2.

    supplementary information S2 (data)500 SNPs (minor allele) in Genaissance panel File name: Genaissance_panel_snps_500.txt Refers to figure: 1c Column 1: Af, African; Eu, European; As, Asian.Missing data indicated by ‘X’.

  3. 3.

    supplementary information S3 (data)250 SNPs (minor allele) in Genaissance panel File name: Genaissance_panel_snps_250.txtRefers to figure: 1d Column 1: Af, African; Eu, European; As, Asian.Missing data indicated by ‘X’.

  4. 4.

    supplementary information S4 (data)377 STRs typed in 1,066 individuals from CEPH diversity panel File name: Rosenberg_ceph_subset_str.txt Refers to figure: 2 Column 1: continent ID (Af, African; Eu, European; As, Asian) and individual ID. Genotypes scored by allele size and alleles at each locus are separated by a ‘.’. Missing data indicated by ‘?’.

  5. 5.

    supplementary information S5 (data)60 STRs typed in Africans, Asians and Europeans File name: Bamshad_continental_str_60.txt Refers to figure: 3b Column 1: Af, African; Eu, European; As, Asian. Column 2: continent code. Columns 3–63: STR genotypes scored by relative size of allele. The genotype of each individual occupies 2 lines of text. Missing data indicated by ‘-9’.

  6. 6.

    supplementary information S6 (data)SNP (minor allele) frequencies from 3,391 genes resequenced in African and European–Americans in Geniassance panel File name: Genaissance_panel_snps_50k.txt Refers to figure: 4 Column 1: q_Af, African; q_Eu, European.



Organization of a population into sub-populations as a consequence of factors such as finite population size and geographical subdivision.


A group of individuals that establishes a new population.


Nonrandom choice of mates based on phenotypic characteristics such as geographical proximity, skin colour, height or religion.


Fluctuations of allele frequencies over time due to chance alone.


A statistic that quantifies the dispersion of data about the mean.


A gradient in the frequency of an allele.


The mixing of two or more genetically differentiated populations.


A measurable trait that depends on the cumulative action of many genes and that can vary among individuals over a given range to produce a continuous distribution of phenotypes. Common examples include height, weight and blood pressure.


A type of natural selection in which favoured variants increase in frequency in a localized geographical region.


This group is defined by variants in a chemokine receptor that is present on the surface of several types of cell, including red blood cells. This receptor must be present for Plasmodium vivax to invade cells and cause malaria.


A process in which traits evolve to a similar state in two or more genetically distinct populations, typically as an adaptive response.


A selection regime that results in the maintenance of two or more alleles at a single locus in a population.


A resource of 1,064 cultured lymphoblastoid cell lines from individuals in 51 different world populations that are banked at the Foundation Jean Dausset (CEPH) in Paris, France.


A statistic similar to FST that is used to estimate differentiation among groups by using microsatellite markers.


The selection of samples (such as markers, individuals, populations) through a process that often deviates from random sampling and can therefore introduce bias.


The combination of alleles or genetic markers that is found on a single chromosome of a given individual.


An autosomal recessive condition that is common in Western Europeans and their descendants. It is characterized by excessive iron absorption by the gut, with subsequent accumulation in the liver, heart, joints and pancreas.


An autosomal recessive condition that is common in Western Europeans and their descendants. It is characterized by pancreatic insufficiency and obstruction of the lungs by thick, heavy mucus.


The proportion of individuals with a specific genotype who manifest this genotype at the phenotype level.


A trait that is influenced by the environment plus a combination of polymorphisms in at least several genes, each of which has a small effect.


A strategy for mapping loci for complex traits that differ in prevalence between two populations that have recently admixed with each other.

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