Human Genetics

, Volume 127, Issue 5, pp 563–572

Population description and its role in the interpretation of genetic association

  • Stephanie M. Fullerton
  • Joon-Ho Yu
  • Julia Crouch
  • Kelly Fryer-Edwards
  • Wylie Burke
Original Investigation

Abstract

Despite calls for greater clarity and precision of population description, studies have documented persistent ambiguity in the use of race/ethnicity terms in genetic research. It is unclear why investigators tolerate such ambiguity, or what effect these practices have on the evaluation of reported associations. To explore the way that population description is used to replicate and/or extend previously reported genetic observations, we examined articles describing the association of the peroxisome proliferator-activated receptor-gamma-γ Pro12Ala polymorphism with type 2 diabetes mellitus and related phenotypes, published between 1997 and 2005. The 80 articles identified were subjected to a detailed content analysis to determine (1) how sampled populations were described, (2) whether and how the choice of sample was explained, and (3) how the allele frequency and genetic association findings identified were contextualized and interpreted. In common with previous reports, we observed a variety of sample descriptions and little explanation for the choice of population investigated. Samples of European origin were typically described with greater specificity than samples of other origin. However, findings from European samples were nearly always compared to samples described as “Caucasian” and sometimes generalized to all Caucasians or to all humans. These findings suggest that care with population description, while important, may not fully address analytical concerns regarding the interpretation of variable study outcomes or ethical concerns regarding the attribution of genetic observations to broad social groups. Instead, criteria which help investigators better distinguish justified and unjustified forms of population generalization may be required.

Supplementary material

439_2010_800_MOESM1_ESM.pdf (47 kb)
Supplementary material (PDF 46.9 kb)

References

  1. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, Lane CR, Schaffner SF, Bolk S, Brewer C, Tuomi T, Gaudet D, Hudson TJ, Daly M, Groop L, Lander ES (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26(1):76–80CrossRefPubMedGoogle Scholar
  2. Anonymous (2000) Census, race and science. Nat Genet 24(2):97–98CrossRefGoogle Scholar
  3. Anonymous (2004) The unexamined ‘Caucasian’. Nat Genet 36(6):541CrossRefGoogle Scholar
  4. Caulfield T, Fullerton SM, Ali-Khan SE, Arbour L, Burchard EG, Cooper RS, Hardy BJ, Harry S, Hyde-Lay R, Kahn J, Kittles R, Koenig BA, Lee SS, Malinowski M, Ravitsky V, Sankar P, Scherer SW, Seguin B, Shickle D, Suarez-Kurtz G, Daar AS (2009) Race and ancestry in biomedical research: exploring the challenges. Genome Med 1(1):8CrossRefPubMedGoogle Scholar
  5. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF Jr, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, Roberts J, Rotimi C, Tucker MA, Vogan KJ, Wacholder S, Wijsman EM, Winn DM, Collins FS (2007) Replicating genotype–phenotype associations. Nature 447(7145):655–660CrossRefPubMedGoogle Scholar
  6. Comstock RD, Castillo EM, Lindsay SP (2004) Four-year review of the use of race and ethnicity in epidemiologic and public health research. Am J Epidemiol 159(6):611–619CrossRefPubMedGoogle Scholar
  7. Deeb SS, Fajas L, Nemoto M, Pihlajamäki J, Mykkänen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20(3):284–287CrossRefPubMedGoogle Scholar
  8. Foster MW (2009) Looking for race in all the wrong places: analyzing the lack of productivity in the ongoing debate about race and genetics. Hum Genet 126(3):355–362CrossRefPubMedGoogle Scholar
  9. Fujimura JH, Duster T, Rajagopalan R (2008) Race, genetics, and disease: questions of evidence, matters of consequence. Soc Stud Sci 38(5):643–656CrossRefPubMedGoogle Scholar
  10. Hsieh HF, Shannon SE (2005) Three approaches to qualitative content analysis. Qual Health Res 15(9):1277–1288CrossRefPubMedGoogle Scholar
  11. Hunt LM, Megyesi MS (2008a) The ambiguous meanings of the racial/ethnic categories routinely used in human genetics research. Soc Sci Med 66:349–361CrossRefPubMedGoogle Scholar
  12. Hunt LM, Megyesi MS (2008b) Genes, race and research ethics: who’s minding the store? J Med Ethics 34:495–500CrossRefPubMedGoogle Scholar
  13. Igl BW, Konig IR, Ziegler A (2009) What do we mean by ‘replication’ and ‘validation’ in genome-wide association studies? Hum Hered 67(1):66–68CrossRefPubMedGoogle Scholar
  14. Ioannidis JP, Boffetta P, Little J, O’Brien TR, Uitterlinden AG, Vineis P, Balding DJ, Chokkalingam A, Dolan SM, Flanders WD, Higgins JP, McCarthy MI, McDermott DH, Page GP, Rebbeck TR, Seminara D, Khoury MJ (2008) Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 37(1):120–132CrossRefPubMedGoogle Scholar
  15. Kaplan JB, Bennett T (2003) Use of race and ethnicity in biomedical publication. JAMA 289(20):2709–2716CrossRefPubMedGoogle Scholar
  16. Lee C (2009) “Race” and “ethnicity” in biomedical research: how do scientists construct and explain differences in health? Soc Sci Med 68(6):1183–1190CrossRefPubMedGoogle Scholar
  17. Lee SS, Mountain J, Koenig B, Altman R, Brown M, Camarillo A, Cavalli-Sforza L, Cho M, Eberhardt J, Feldman M, Ford R, Greely H, King R, Markus H, Satz D, Snipp M, Steele C, Underhill P (2008) The ethics of characterizing difference: guiding principles on using racial categories in human genetics. Genome Biol 9(7):404 (Epub Jul 15)CrossRefPubMedGoogle Scholar
  18. Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, Scheet P, Gwinn M, Williamson RE, Zou GY, Hutchings K, Johnson CY, Tait V, Wiens M, Golding J, van Duijn C, McLaughlin J, Paterson A, Wells G, Fortier I, Freedman M, Zecevic M, King R, Infante-Rivard C, Stewart A, Birkett N (2009) Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement. Hum Genet 125(2):131–151CrossRefPubMedGoogle Scholar
  19. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, Hirschhorn JN (2008) Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 9(5):356–369CrossRefPubMedGoogle Scholar
  20. Outram SM, Ellison G (2006) Anthropological insights into the use of race/ethnicity to explore genetic contributions to disparities in health. J Biosoc Sci 32:83–102Google Scholar
  21. Race, Ethnicity, and Genetics Working Group (2005) The use of racial, ethnic, and ancestral categories in human genetics research. Am J Hum Genet 77(4):519–532Google Scholar
  22. Sankar P (2006) Hasty generalisation and exaggerated certainties: reporting genetic findings in health disparities research. New Genet Soc 25(3):249–264CrossRefGoogle Scholar
  23. Sankar P, Cho MK (2002) Genetics. Toward a new vocabulary of human genetic variation. Science 298(5597):1337–1338CrossRefPubMedGoogle Scholar
  24. Sankar P, Cho MK, Mountain J (2007) Race and ethnicity in genetic research. Am J Med Genet 143A(9):961–970CrossRefPubMedGoogle Scholar
  25. Shanawani H, Dame L, Schwartz DA, Cook-Deegan R (2006) Non-reporting and inconsistent reporting of race and ethnicity in articles that claim associations among genotype, outcome, and race or ethnicity. J Med Ethics 32(12):724–728CrossRefPubMedGoogle Scholar
  26. Shields AE, Fortun M, Hammonds EM, King PA, Lerman C, Rapp R, Sullivan PF (2005) The use of race variables in genetic studies of complex traits and the goal of reducing health disparities: a transdisciplinary perspective. Am Psychol 60(1):77–103CrossRefPubMedGoogle Scholar
  27. Smart A, Tutton R, Ashcroft R, Martin PA, Ellison GTH (2006) Can science alone improve the measurement and communication of race and ethnicity in genetic research? Exploring the strategies proposed by Nature Genetics. BioSocieties 1(3):313–324CrossRefGoogle Scholar
  28. Smart A, Tutton R, Martin P, Ellison GT, Ashcroft R (2008) The standardization of race and ethnicity in biomedical science editorials and UK biobanks. Soc Stud Sci 38(3):407–423CrossRefPubMedGoogle Scholar
  29. Weber RP (1990) Basic content analysis. Sage, Beverly HillsGoogle Scholar
  30. Yen C, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, Burns DK, Roth J, Shuldiner AR (1997) Molecular scanning of the human peroxisome proliferator activated receptor g (hPPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ2 missense mutation. Biochem Biophys Res Commun 241:270–274CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Stephanie M. Fullerton
    • 1
  • Joon-Ho Yu
    • 1
  • Julia Crouch
    • 1
  • Kelly Fryer-Edwards
    • 1
  • Wylie Burke
    • 1
  1. 1.Department of Bioethics and Humanities, Center for Genomics and Healthcare EqualityUniversity of Washington School of MedicineSeattleUSA

Personalised recommendations