Skip to main content

Analysis of Genome-Wide Association Data

  • Protocol
  • First Online:
Bioinformatics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1526))

Abstract

The last decade has seen substantial advances in the understanding of the genetics of complex traits and disease. This has been largely driven by genome-wide association studies (GWAS), which have identified thousands of genetic loci associated with these traits and disease. This chapter provides a guide on how to perform GWAS on both binary (case–control) and quantitative traits. As poor data quality, through both genotyping failures and unobserved population structure, is a major cause of false-positive genetic associations, there is a particular focus on the crucial steps required to prepare the SNP data prior to analysis. This is followed by the methods used to perform the actual GWAS and visualization of the results.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
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

Institutional subscriptions

References

  1. Stranger BE, Stahl EA, Raj T (2011) Progress and promise of genome-wide association studies for human complex trait genetics. Genetics 187:367–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H et al (2014) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42:D1001–D1006

    Article  CAS  PubMed  Google Scholar 

  3. Dewan A, Liu M, Hartman S, Zhang SS-M, Liu DTL, Zhao C et al (2006) HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 314(5801):989–992

    Article  CAS  PubMed  Google Scholar 

  4. Klein RJ, Zeiss C, Chew EY, Tsai J-Y, Sackler RS, Haynes C et al (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308(5720):385–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678

    Article  PubMed Central  Google Scholar 

  6. Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Clayton DG, Walker NM, Smyth DJ, Pask R, Cooper JD, Maier LM et al (2005) Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet 37(11):1243–1246

    Article  CAS  PubMed  Google Scholar 

  8. Anderson CA, Pettersson FH, Clarke GM, Cardon LR, Morris AP, Zondervan KT (2010) Data quality control in genetic case-control association studies. Nat Protoc 5(9):1564–1573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rabbee N, Speed TP (2006) A genotype calling algorithm for affymetrix SNP arrays. Bioinformatics 22(1):7–12

    Article  CAS  PubMed  Google Scholar 

  10. Teo YY, Inouye M, Small KS, Gwilliam R, Deloukas P, Kwiatkowski DP et al (2007) A genotype calling algorithm for the Illumina BeadArray platform. Bioinformatics 23(20):2741–2746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cardon LR, Palmer LJ (2003) Population stratification and spurious allelic association. Lancet 361:598–604

    Article  PubMed  Google Scholar 

  12. Campbell CD, Ogburn EL, Lunetta KL, Lyon HN, Freedman ML, Groop LC et al (2005) Demonstrating stratification in a European American population. Nat Genet 37(8):868–872

    Article  CAS  PubMed  Google Scholar 

  13. The International HapMap 3 Consortium (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467:52–58

    Article  PubMed Central  Google Scholar 

  14. Turner S, Armstrong LL, Bradford Y, Carlson CS, Crawford DC, Crenshaw AT et al (2011) Quality control procedures for genome-wide association studies. Curr Protoc Hum Genet Chapter 1, Unit 1.19

    Google Scholar 

  15. Wittke-Thompson JK, Pluzhnikov A, Cox NJ (2005) Rational inferences about departures from Hardy-Weinberg equilibrium. Am J Hum Genet 76(6):967–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Spencer CCA, Su Z, Donnelly P, Marchini J (2009) Designing genome-wide association studies: Sample size, power, imputation, and the choice of genotyping chip. PLoS Genet 5(5):e1000477

    Article  PubMed  PubMed Central  Google Scholar 

  17. The 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491(7422):56–65

    Article  PubMed Central  Google Scholar 

  18. Marchini J, Howie B (2010) Genotype imputation for genome-wide association studies. Nat Rev Genet 11(7):499–511

    Article  CAS  PubMed  Google Scholar 

  19. Howie B, Marchini J, Stephens M (2011) Genotype imputation with thousands of genomes. G3 1(6):457–470

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pe’er I, Yelensky R, Altshuler D, Daly MJ (2008) Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32(4):381–385

    Article  PubMed  Google Scholar 

  21. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G et al (2007) Replicating genotype-phenotype associations. Nature 447(7145):655–660

    Article  CAS  PubMed  Google Scholar 

  22. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38(8):904–909

    Article  CAS  PubMed  Google Scholar 

  24. Delaneau O, Marchini J, Zagury J-F (2011) A linear complexity phasing method for thousands of genomes. Nat Methods 9(2):179–181

    Article  PubMed  Google Scholar 

  25. Delaneau O, Howie B, Cox AJ, Zagury JF, Marchini J (2013) Haplotype estimation using sequencing reads. Am J Hum Genet 93(4):687–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet 44(8):955–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Allan F. McRae .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media New York

About this protocol

Cite this protocol

McRae, A.F. (2017). Analysis of Genome-Wide Association Data. In: Keith, J. (eds) Bioinformatics. Methods in Molecular Biology, vol 1526. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6613-4_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6613-4_9

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6611-0

  • Online ISBN: 978-1-4939-6613-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics