Advertisement

Association Mapping and Disease: Evolutionary Perspectives

  • Søren Besenbacher
  • Thomas Mailund
  • Mikkel H. Schierup
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 856)

Abstract

In this chapter, we give a short introduction to the genetics of complex disease with special emphasis on evolutionary models for disease genes and the effect of different models on the genetic architecture, and finally give a survey of the state-of-the-art of genome-wide association studies.

Key words

Complex diseases Association mapping Genome-wide association studies Common disease/common variant 

References

  1. 1.
    Visscher PM, Hill WG, Wray NR (2008) Heritability in the genomics era – concepts and misconceptions. Nat Rev Genet 9: 255–266.PubMedCrossRefGoogle Scholar
  2. 2.
    Cardon LR, Abecasis GR (2003) Using haplotype blocks to map human complex trait loci. Trends Genet 19: 135–140.PubMedCrossRefGoogle Scholar
  3. 3.
    de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, et al. (2005) Efficiency and power in genetic association studies. Nat Genet 37: 1217–1223.PubMedCrossRefGoogle Scholar
  4. 4.
    Daly MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES (2001) High-resolution haplotype structure in the human genome. Nat Genet 29: 229–232.PubMedCrossRefGoogle Scholar
  5. 5.
    Maher B (2008) Personal genomes: The case of the missing heritability. Nature 456: 18–21.PubMedCrossRefGoogle Scholar
  6. 6.
    Wright S (1931) Evolution in Mendelian populations. Genetics 16: 97–159.PubMedGoogle Scholar
  7. 7.
    Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69: 124–137.PubMedCrossRefGoogle Scholar
  8. 8.
    Pritchard JK, Cox NJ (2002) The allelic architecture of human disease genes: common disease-common variant…or not? Hum Mol Genet 11: 2417–2423.PubMedCrossRefGoogle Scholar
  9. 9.
    Reich DE, Lander ES (2001) On the allelic spectrum of human disease. Trends Genet 17: 502–510.PubMedCrossRefGoogle Scholar
  10. 10.
    Di Rienzo A, Hudson RR (2005) An evolutionary framework for common diseases: the ancestral-susceptibility model. Trends Genet 21: 596–601.PubMedCrossRefGoogle Scholar
  11. 11.
    Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, et al. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861.PubMedCrossRefGoogle Scholar
  12. 12.
    Durbin RM, Abecasis GR, Altshuler DL, Auton A, Brooks LD, et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467: 1061–1073.CrossRefGoogle Scholar
  13. 13.
    Gorlov IP, Gorlova OY, Sunyaev SR, Spitz MR, Amos CI (2008) Shifting paradigm of association studies: value of rare single-nucleotide polymorphisms. Am J Hum Genet 82: 100–112.PubMedCrossRefGoogle Scholar
  14. 14.
    Li Y, Vinckenbosch N, Tian G, Huerta-Sanchez E, Jiang T, et al. (2010) Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. Nat Genet 42: 969–972.PubMedCrossRefGoogle Scholar
  15. 15.
    Pelak K, Shianna KV, Ge D, Maia JM, Zhu M, et al. (2010) The characterization of twenty sequenced human genomes. PLoS Genet 6.Google Scholar
  16. 16.
    Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, et al. (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308: 385–389.PubMedCrossRefGoogle Scholar
  17. 17.
    Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, et al. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314: 1461–1463.PubMedCrossRefGoogle Scholar
  18. 18.
    Lewis CM (2002) Genetic association studies: design, analysis and interpretation. Brief Bioinform 3: 146–153.PubMedCrossRefGoogle Scholar
  19. 19.
    Balding DJ (2006) A tutorial on statistical methods for population association studies. Nat Rev Genet 7: 781–791.PubMedCrossRefGoogle Scholar
  20. 20.
    WTCCC (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678.CrossRefGoogle Scholar
  21. 21.
    McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, et al. (2008) Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 9: 356–369.PubMedCrossRefGoogle Scholar
  22. 22.
    Patterson N, Price AL, Reich D (2006) Population structure and eigenanalysis. PLoS Genet 2: e190.Google Scholar
  23. 23.
    Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55: 997–1004.PubMedCrossRefGoogle Scholar
  24. 24.
    Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, et al. (2010) Genetic Signatures of Exceptional Longevity in Humans. Science.Google Scholar
  25. 25.
    Alberts B (2010) Editorial expression of concern. Science 330(6006): 912. DOI: 10.1126/science.330.6006.912-b.Google Scholar
  26. 26.
    Teo YY, Small KS, Kwiatkowski DP (2010) Methodological challenges of genome-wide association analysis in Africa. Nat Rev Genet 11: 149–160.PubMedCrossRefGoogle Scholar
  27. 27.
    Zaitlen N, Pasaniuc B, Gur T, Ziv E, Halperin E (2010) Leveraging genetic variability across populations for the identification of causal variants. Am J Hum Genet 86: 23–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Marchini J, Howie B (2010) Genotype imputation for genome-wide association studies. Nat Rev Genet 11: 499–511.PubMedCrossRefGoogle Scholar
  29. 29.
    Sudmant PH, Kitzman JO, Antonacci F, Alkan C, Malig M, et al. (2010) Diversity of human copy number variation and multicopy genes. Science 330: 641–646.PubMedCrossRefGoogle Scholar
  30. 30.
    Marchini J, Howie B, Myers S, McVean G, Donnelly P (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39: 906–913.PubMedCrossRefGoogle Scholar
  31. 31.
    Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34: 816–834.PubMedCrossRefGoogle Scholar
  32. 32.
    Scheet P, Stephens M (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78: 629–644.PubMedCrossRefGoogle Scholar
  33. 33.
    Servin B, Stephens M (2007) Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet 3: e114.PubMedCrossRefGoogle Scholar
  34. 34.
    Nothnagel M, Ellinghaus D, Schreiber S, Krawczak M, Franke A (2009) A comprehensive evaluation of SNP genotype imputation. Hum Genet 125: 163–171.PubMedCrossRefGoogle Scholar
  35. 35.
    Guan Y, Stephens M (2008) Practical issues in imputation-based association mapping. PLoS Genet 4: e1000279.PubMedCrossRefGoogle Scholar
  36. 36.
    Stephens M, Balding DJ (2009) Bayesian statistical methods for genetic association studies. Nat Rev Genet 10: 681–690.PubMedCrossRefGoogle Scholar
  37. 37.
    Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, et al. (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106: 9362–9367.PubMedCrossRefGoogle Scholar
  38. 38.
    Iles MM (2008) What can genome-wide association studies tell us about the genetics of common disease? PLoS Genet 4: e33.PubMedCrossRefGoogle Scholar
  39. 39.
    Kryukov GV, Pennacchio LA, Sunyaev SR (2007) Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am J Hum Genet 80: 727–739.PubMedCrossRefGoogle Scholar
  40. 40.
    Li B, Leal SM (2008) Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet 83: 311–321.PubMedCrossRefGoogle Scholar
  41. 41.
    Madsen BE, Browning SR (2009) A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet 5: e1000384.PubMedCrossRefGoogle Scholar
  42. 42.
    Morris AP, Zeggini E (2010) An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet Epidemiol 34: 188–193.PubMedCrossRefGoogle Scholar
  43. 43.
    Price AL, Kryukov GV, de Bakker PI, Purcell SM, Staples J, et al. (2010) Pooled association tests for rare variants in exon-resequencing studies. Am J Hum Genet 86: 832–838.PubMedCrossRefGoogle Scholar
  44. 44.
    Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB (2010) Rare variants create synthetic genome-wide associations. PLoS Biol 8:e1000294.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Søren Besenbacher
    • 1
    • 2
  • Thomas Mailund
    • 2
  • Mikkel H. Schierup
    • 2
  1. 1.deCODE GeneticsReykjavikIceland
  2. 2.Bioinformatics Research CenterAarhus UniversityAarhusDenmark

Personalised recommendations