Skip to main content
SpringerLink
Log in
Book cover

Evolutionary Genomics pp 275–291Cite as

Association Mapping and Disease: Evolutionary Perspectives

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((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.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Visscher PM, Hill WG, Wray NR (2008) Heritability in the genomics era – concepts and misconceptions. Nat Rev Genet 9: 255–266.

    Article  PubMed  CAS  Google Scholar 

  2. Cardon LR, Abecasis GR (2003) Using haplotype blocks to map human complex trait loci. Trends Genet 19: 135–140.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  5. Maher B (2008) Personal genomes: The case of the missing heritability. Nature 456: 18–21.

    Article  PubMed  CAS  Google Scholar 

  6. Wright S (1931) Evolution in Mendelian populations. Genetics 16: 97–159.

    PubMed  CAS  Google Scholar 

  7. Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69: 124–137.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  9. Reich DE, Lander ES (2001) On the allelic spectrum of human disease. Trends Genet 17: 502–510.

    Article  PubMed  CAS  Google Scholar 

  10. Di Rienzo A, Hudson RR (2005) An evolutionary framework for common diseases: the ancestral-susceptibility model. Trends Genet 21: 596–601.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  18. Lewis CM (2002) Genetic association studies: design, analysis and interpretation. Brief Bioinform 3: 146–153.

    Article  PubMed  CAS  Google Scholar 

  19. Balding DJ (2006) A tutorial on statistical methods for population association studies. Nat Rev Genet 7: 781–791.

    Article  PubMed  CAS  Google Scholar 

  20. WTCCC (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  22. Patterson N, Price AL, Reich D (2006) Population structure and eigenanalysis. PLoS Genet 2: e190.

    Google Scholar 

  23. Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55: 997–1004.

    Article  PubMed  CAS  Google Scholar 

  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. Alberts B (2010) Editorial expression of concern. Science 330(6006): 912. DOI: 10.1126/science.330.6006.912-b.

    Google Scholar 

  26. Teo YY, Small KS, Kwiatkowski DP (2010) Methodological challenges of genome-wide association analysis in Africa. Nat Rev Genet 11: 149–160.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  28. Marchini J, Howie B (2010) Genotype imputation for genome-wide association studies. Nat Rev Genet 11: 499–511.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  33. Servin B, Stephens M (2007) Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet 3: e114.

    Article  PubMed  Google Scholar 

  34. Nothnagel M, Ellinghaus D, Schreiber S, Krawczak M, Franke A (2009) A comprehensive evaluation of SNP genotype imputation. Hum Genet 125: 163–171.

    Article  PubMed  CAS  Google Scholar 

  35. Guan Y, Stephens M (2008) Practical issues in imputation-based association mapping. PLoS Genet 4: e1000279.

    Article  PubMed  Google Scholar 

  36. Stephens M, Balding DJ (2009) Bayesian statistical methods for genetic association studies. Nat Rev Genet 10: 681–690.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  38. Iles MM (2008) What can genome-wide association studies tell us about the genetics of common disease? PLoS Genet 4: e33.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  41. Madsen BE, Browning SR (2009) A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet 5: e1000384.

    Article  PubMed  Google Scholar 

  42. Morris AP, Zeggini E (2010) An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet Epidemiol 34: 188–193.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  44. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB (2010) Rare variants create synthetic genome-wide associations. PLoS Biol 8:e1000294.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. deCODE Genetics, Reykjavik, Iceland

    Søren Besenbacher

  2. Bioinformatics Research Center, Aarhus University, Aarhus, Denmark

    Søren Besenbacher, Thomas Mailund & Mikkel H. Schierup

Authors
  1. Søren Besenbacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Mailund
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mikkel H. Schierup
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Mailund .

Editor information

Editors and Affiliations

  1. Department of Computer Science, ETH Zürich, Universitätsstr. 6, Zürich, 8092, Switzerland

    Maria Anisimova

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Besenbacher, S., Mailund, T., Schierup, M.H. (2012). Association Mapping and Disease: Evolutionary Perspectives. In: Anisimova, M. (eds) Evolutionary Genomics. Methods in Molecular Biology, vol 856. Humana Press. https://doi.org/10.1007/978-1-61779-585-5_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-585-5_11

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-584-8

  • Online ISBN: 978-1-61779-585-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation