Genetic Epidemiology of Complex Phenotypes

  • Lynette Peddle
  • Proton RahmanEmail author
Part of the Methods in Molecular Biology™ book series (MIMB, volume 473)


Genetic factors play a substantive role in the susceptibility to common diseases. Due to recent advancements in the characterization of genetic variants and large-scale genotyping platforms, multiple genes have now been identified for common, complex diseases. As a result, there is an immense interest in elucidating genetic factors in complex traits. Therefore, it is important to understand the design as well as the technical and statistical issues of the two most common approaches for gene identification: linkage and association.

Key words

Genetic epidemiology linkage studies association studies whole genomewide association scans genotyping linkage disequilibrium 


  1. 1.
    1. Lander, E. S., Schork, N. J. (1994) Genetic dissection of complex traits. Science 265, 2037–2047.PubMedCrossRefGoogle Scholar
  2. 2.
    2. Newton-Cheh, C., Hirschhorn, J. N. (2005) Genetic association studies of complex traits: Design and analysis issues. Mutation Res 573, 54–69.PubMedCrossRefGoogle Scholar
  3. 3.
    3. Ghosh, S., Collins, F. S. (1996) The geneticist's approach to complex disease. Ann Rev Med 47, 333–353.PubMedCrossRefGoogle Scholar
  4. 4.
    4. Hirschhorn, J. N. (2005) Genetic approaches to studying common diseases and complex traits. Pediatrics Res 57 (5), 74–77.CrossRefGoogle Scholar
  5. 5.
    5. Risch, N.(1997) Genetic linkage from an epidemiological perspective. Epidemiol Rev 19, 24–32.PubMedGoogle Scholar
  6. 6.
    6. Bandrup, F. (1982) Psoriasis in monozygotic twins. Variations in expression of individuals with identical genetic constitution. Acta Dermatol 62, 229–236.Google Scholar
  7. 7.
    7. Farber, E. M., Nail, L., et al. (1974). Natural history of psoriasis in 61 twin pairs. Arch Dermatol 1 (9), 207–211.CrossRefGoogle Scholar
  8. 8.
    8. Risch, N. (1990) Linkage strategies for genetically complex traits, 1. Multilocus model. Am J Hum Genet 46, 222–228.PubMedGoogle Scholar
  9. 9.
    9. Heneseler, T. (1997) The genetics of psoriasis. J Am Acad Dermatol 37, S1—S11.Google Scholar
  10. 10.
    10. Sherman, S. L. (1997) Evolving methods in genetic epidemiology, IV. Approaches to non-Mendelian inheritance. Epidemiol Rev 19: (1), 44–51.PubMedGoogle Scholar
  11. 11.
    11. Harper, P. S., Harley, H. G., Reardon, W., et al. (1992) Anticipation in myotonic dystrophy: New insights on an old problem. Am J Hum Genet 51, 10–16.PubMedGoogle Scholar
  12. 12.
    12. Hall, J. G. (1990) Genomic imprinting: Review and relevance to human diseases. Am J Hum Genet 46, 857–873.PubMedGoogle Scholar
  13. 13.
    13. Langlois, S., Lopez-Rangel, E., Hall, J. G. (1995) New mechanisms for genetic disease and nontraditional modes of inheritance. Adv Pediatric 42, 91–111.Google Scholar
  14. 14.
    14. Rahman, P., Gladman, D. D., Schentag, C. T., Petronis, A. (1999) Excessive paternal transmission in psoriatic arthritis. Arthritis Rheum 42 (6), 1228–1231.PubMedCrossRefGoogle Scholar
  15. 15.
    15. Wallace, D. C. (1992) Disease of the mitochondrial DNA. Ann Rev Biochem 61, 1175–1212.PubMedCrossRefGoogle Scholar
  16. 16.
    16. Sham, P. (1998) Statistics in Human Genetics. John Wiley & Sons, London.Google Scholar
  17. 17.
    17. Kruglyak, L., Daly, M. J., Reeve-Daly, M. P., et al. (1996) Parametic and nonparametric linkage analysis: A unified multipoint approach. Am J Hum Genet 58, 1347–1363.PubMedGoogle Scholar
  18. 18.
    18. Ott J. (1999) Analysis of Human Genetic Linkage, 3rd ed. Johns Hopkins University Press, Baltimore, MD.Google Scholar
  19. 19.
    19. Nagase, H. (1993) Mutations of the APC gene. Hum Mut 2, 425–434.PubMedCrossRefGoogle Scholar
  20. 20.
    20. Morton, N. E. (1955) Sequential tests for detection of linkage. Am J Hum Genet 7, 277–318.PubMedGoogle Scholar
  21. 21.
    21. Lander, E., Kruglyak, L. (1995) Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results. Nat Genet 11, 241–247.PubMedCrossRefGoogle Scholar
  22. 22.
    22. Risch, N. (1990) Linkage strategies for complex traits, II. The power of affected relative pairs. Am J Hum Genet 46, 219–221.Google Scholar
  23. 23.
    23. The International HapMap Consortium. (2003) The international HapMap project. Nature 426, 789–796CrossRefGoogle Scholar
  24. 24.
    24. Gottesman, I, I,, Gould, T. D. (2003) The endophenotype concept in psychiatry: Etymology and strategic intentions. Am J Psychiatry 160 (4), 636–645.PubMedCrossRefGoogle Scholar
  25. 25.
    25. Cordell, H. J., Clayton, D. G. (2005) Genetic Epidemiology, 3: Genetic association studies. Lancet 366:1121–1131PubMedCrossRefGoogle Scholar
  26. 26.
    26. Ehm, M. G., Nelson, M. R., Spurr, N. K. (2005) Guidelines for conducting and reporting whole genome/large scale association studies. Hum Molec Genet 14 (17), 2485–2488.PubMedCrossRefGoogle Scholar
  27. 27.
    27. Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., et al. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314 (5804),1461–1463.PubMedCrossRefGoogle Scholar
  28. 28.
    28. Huizinga, T. W. J., Pisetsky, D. S., Kimberly, R. P. (2004) Associations, populations, truth. Arthritis Rheum 50 (7),2066–2071.PubMedCrossRefGoogle Scholar
  29. 29.
    29. Hischhorn, J. N., Lohmueller, K., Byrne, E., Hischhorn, K. (2002) A comprehensive review of genetic association studies. Genet Med 4, 45–61.CrossRefGoogle Scholar
  30. 30.
    30. Hirschhorn, J. N., Daly, M. J. (2005) Genome wide association studies for common diseases and complex traits. Nature Rev 6, 95–108.Google Scholar
  31. 31.
    31. Freimer, N. B., Sabatti, C. (2005) Guidelines for association studies. Hum Molec Genet. 14 (17), 2481–2483.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Senior Scientist, Newfound GenomicsCanada
  2. 2.St. Clares HospitalNewfoundlandCanada

Personalised recommendations