Skip to main content

Identifying Cryptic Relationships

  • Protocol
  • First Online:
Statistical Human Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1666))

Abstract

Cryptic relationships such as first-degree relatives often appear in studies that collect population samples, including genome-wide association studies (GWAS) and next-generation sequencing (NGS) analyses. Cryptic relatedness not only increases type 1 error rate of association tests but also affects other analytical aspects of GWAS and NGS such as population stratification via principal component analysis. Here, we discuss three effective methods, as implemented in PREST, PLINK, and KING, to detect and correct for the problem of cryptic relatedness using high-throughput SNP data collected from GWAS and NGS experiments. We provide the analytical and practical details involved using three application examples.

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

Access this chapter

Institutional subscriptions

Similar content being viewed by others

References

  1. Voight BF, Pritchard JK (2005) Confounding from cryptic relatedness in case-control association studies. PLoS Genet 1(3):e32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thornton T, McPeek MS (2010) Roadtrips: case-control association testing with partially or completely unknown population and pedigree structure. Am J Hum Genet 86(2):172–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Price AL, Zaitlen NA, Reich D, Patterson N (2010) New approaches to population stratification in genome-wide association studies. Nat Rev Genet 11:459–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. McPeek MS, Sun L (2000) Statistical tests for detection of misspecified relationships by use of genome-screen data. Am J Hum Genet 66(3):1076–1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dimitromanolakis A, Paterson AD, Sun L (2009) Accurate IBD inference identifies cryptic relatedness in 9 hapmap populations. Abstract no. 1768 presented at the annual meeting of the American Society of Human Genetics.

    Google Scholar 

  6. Sun L, Wilder K, McPeek MS (2002) Enhanced pedigree error detection. Hum Hered 54(2):99–110

    Article  PubMed  Google Scholar 

  7. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC (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 

  8. Manichaikul A, Mychaleckyj JC, Rich SS, Daly K, Sale M, Chen WM (2010) Robust relationship inference in genome-wide association studies. Bioinformatics 56(22):2867–2873

    Article  CAS  Google Scholar 

  9. Chen WM, Manichaikul A, Rich SS (2016) KING 2.0: relationship inference and integrated analysis in one million samples. Abstract #365T presented at the American Society of Human Genetics annual meeting

    Google Scholar 

  10. The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million snps. Nature 449(7164):851–861

    Article  CAS  PubMed Central  Google Scholar 

  11. Begleiter H, Reich T, Nurnberger JJ, Li TK, Conneally PM, Edenberg H, Crowe R, Kuperman S, Schuckit M, Bloom F, Hesselbrock V, Porjesz B, Cloninger CR, Rice J, Goate A (1999) Description of the genetic analysis workshop 11 collaborative study on the genetics of alcoholism. Genet Epidemiol 17(Suppl 1):S25–S30

    Article  PubMed  Google Scholar 

  12. Antoni G, Morange P, Luo Y, Saut N, Burgos G, Heath S, Germain M, Biron-Andreani C, Schved J, Pernod G, Galan P, Zelenika D, Alessi M, Drouet L, Visvikis-Siest S, Wells P, Lathrop M, Emmerich J, Tregouet D, Gagnon F (2010) A multi-stage multi-design strategy provides strong evidence that the bai3 locus is associated with early-onset venous thromboembolism. J Thromb Haemost 8(12). doi:10.1111/j.1538-7836.2010.04092.x

  13. Browning SR, Browning BL (2010) High-resolution detection of identity by descent in unrelated individuals. Am J Hum Genet 86(4):526–539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lei Sun .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Sun, L., Dimitromanolakis, A., Chen, WM. (2017). Identifying Cryptic Relationships. In: Elston, R. (eds) Statistical Human Genetics. Methods in Molecular Biology, vol 1666. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7274-6_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7274-6_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7273-9

  • Online ISBN: 978-1-4939-7274-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics