Skip to main content

Imputation-Based HLA Typing with SNPs in GWAS Studies

  • Protocol
  • First Online:
HLA Typing

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1802))

Abstract

SNP-based imputation approaches for human leukocyte antigen (HLA) typing take advantage of the extended haplotype structure within the major histocompatibility complex (MHC) to predict classical HLA alleles using dense SNP genotypes, such as those available on chip panels of genome-wide association study (GWAS). These methods enable HLA analyses of classical alleles on existing SNP datasets genotyped in GWAS studies at no extra cost. Here, I describe the workflow of HIBAG, an imputation method with attribute bagging, for obtaining a sample’s HLA class I and II genotypes of two-field resolution using SNP data. Two examples are provided to illustrate with a publicly available HLA and SNP dataset: genotype imputation with pre-fit classifiers in GWAS, and model training to build a new classifier.

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
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

Institutional subscriptions

References

  1. Shiina T, Hosomichi K, Inoko H, Kulski JK (2009) The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54(1):15–39

    Article  CAS  PubMed  Google Scholar 

  2. Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L et al (2014) The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42(Database issue):D1001–D1006

    Article  CAS  PubMed  Google Scholar 

  3. Bauer DC, Zadoorian A, Wilson LO, Thorne NP, Alliance MGH (2016) Evaluation of computational programs to predict HLA genotypes from genomic sequencing data. Brief Bioinform pii:bbw097

    Article  Google Scholar 

  4. Erlich H (2012) HLA DNA typing: past, present, and future. Tissue Antigens 80(1):1–11

    Article  CAS  PubMed  Google Scholar 

  5. Meyer D, Nunes K (2017) HLA imputation, what is it good for? Hum Immunol 78(3):239–241

    Article  PubMed  Google Scholar 

  6. Zheng X, Shen J, Cox C, Wakefield JC, Ehm MG, Nelson MR, Weir BS (2014) HIBAG–HLA genotype imputation with attribute bagging. Pharmacogenomics J 14(2):192–200

    Article  CAS  PubMed  Google Scholar 

  7. Breiman L (1996) Bagging predictors. Mach Learn 24:123–140

    Google Scholar 

  8. Breiman L (2001) Random forests. Mach Learn 45(1):5–32

    Article  Google Scholar 

  9. Khor SS, Yang W, Kawashima M, Kamitsuji S, Zheng X, Nishida N, Sawai H, Toyoda H, Miyagawa T, Honda M et al (2015) High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references. Pharmacogenomics J 15(6):530–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Levin AM, Adrianto I, Datta I, Iannuzzi MC, Trudeau S, McKeigue P, Montgomery CG, Rybicki BA (2014) Performance of HLA allele prediction methods in African Americans for class II genes HLA-DRB1, -DQB1, and -DPB1. BMC Genet 15:72

    Article  PubMed  PubMed Central  Google Scholar 

  11. Nunes K, Zheng X, Torres M, Moraes ME, Piovezan BZ, Pontes GN, Kimura L, Carnavalli JE, Mingroni Netto RC, Meyer D (2016) HLA imputation in an admixed population: an assessment of the 1000 genomes data as a training set. Hum Immunol 77(3):307–312

    Article  CAS  PubMed  Google Scholar 

  12. Pappas DJ, Lizee A, Paunic V, Beutner KR, Motyer A, Vukcevic D, Leslie S, Biesiada J, Meller J, Taylor KD et al (2017) Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest. Pharmacogenomics J. https://doi.org/10.1038/tpj.2017.7

  13. Gourraud PA, Khankhanian P, Cereb N, Yang SY, Feolo M, Maiers M, Rioux JD, Hauser S, Oksenberg J (2014) HLA diversity in the 1000 genomes dataset. PLoS One 9(7):e97282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ 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 

  15. Zheng X, Levine D, Shen J, Gogarten SM, Laurie C, Weir BS (2012) A high-performance computing toolset for relatedness and principal component analysis of SNP data. Bioinformatics 28(24):3326–3328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SG (2015) The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res 43(Database issue):D423–D431

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiuwen Zheng .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Zheng, X. (2018). Imputation-Based HLA Typing with SNPs in GWAS Studies. In: Boegel, S. (eds) HLA Typing. Methods in Molecular Biology, vol 1802. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8546-3_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8546-3_11

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8545-6

  • Online ISBN: 978-1-4939-8546-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics