Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles

Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles Publisher Pubmed

Degenhardt F¹ ; Wendorff M¹ ; Wittig M¹ ; Ellinghaus E² ; Datta LW³ ; Schembri J⁴ ; Ng SC⁵ ; Rosati E¹ ; Hubenthal M¹ ; Ellinghaus D¹ ; Jung ES^{1, 6} ; Lieb W⁷ ; Abedian S^{8, 9} ; Malekzadeh R⁹ Show All Authors

Degenhardt F¹
Wendorff M¹
Wittig M¹
Ellinghaus E²
Datta LW³
Schembri J⁴
Ng SC⁵
Rosati E¹
Hubenthal M¹
Ellinghaus D¹
Jung ES^{1, 6}
Lieb W⁷
Abedian S^{8, 9}
Malekzadeh R⁹
Cheon JH⁶
Ellul P⁴
Sood A¹⁰
Midha V^{10, 11}
Thelma BK¹²
Wong SH⁵
Schreiber S^{1, 13}
Yamazaki K^{14, 15}
Kubo M¹⁶
Boucher G¹⁷
Rioux JD^{17, 18}
Lenz TL¹⁹
Brant SR^{3, 20, 21}
Franke A¹

Show Affiliations

1. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Rosalind-Franklin-Street 12, Kiel, D-24105, Germany
2. K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway
3. Department of Medicine, Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
4. Division of Gastroenterology, Mater Dei Hospital, Msida MSD, Malta
5. Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong, Hong Kong
6. Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
7. Biobank PopGen and Institute of Epidemiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
8. Department of Epidemiology, University Medical Center Groningen, RB Groningen, Netherlands
9. Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
10. Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
11. Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
12. Department of Genetics, University of Delhi South Campus, New Delhi, India
13. Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany
14. Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan
15. Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan
16. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
17. Montreal Heart Institute, Research Center, Montreal, QC, Canada
18. Universite de Montreal Department of Medicine, Montreal, QC, Canada
19. Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, Plon, Germany
20. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
21. Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States

Source: Human Molecular Genetics Published:2019

Abstract

Genotype imputation of the human leukocyte antigen (HLA) region is a cost-effective means to infer classical HLA alleles from inexpensive and dense SNP array data. In the research setting, imputation helps avoid costs for wet lab-based HLA typing and thus renders association analyses of the HLA in large cohorts feasible. Yet, most HLA imputation reference panels target Caucasian ethnicities and multi-ethnic panels are scarce. We compiled a high-quality multi-ethnic reference panel based on genotypes measured with Illumina's Immunochip genotyping array and HLA types established using a high-resolution next generation sequencing approach. Our reference panel includes more than 1,300 samples from Germany, Malta, China, India, Iran, Japan and Korea and samples of African American ancestry for all classical HLA class I and II alleles including HLA-DRB3/4/5. Applying extensive cross-validation, we benchmarked the imputation using the HLA imputation tool HIBAG, our multi-ethnic reference and an independent, previously published data set compiled of subpopulations of the 1000 Genomes project. We achieved average imputation accuracies higher than 0.924 for the commonly studied HLA-A, -B, -C, -DQB1 and -DRB1 genes across all ethnicities. We investigated allele-specific imputation challenges in regard to geographic origin of the samples using sensitivity and specificity measurements as well as allele frequencies and identified HLA alleles that are challenging to impute for each of the populations separately. In conclusion, our new multi-ethnic reference data set allows for high resolution HLA imputation of genotypes at all classical HLA class I and II genes including the HLA-DRB3/4/5 loci based on diverse ancestry populations. © 2018 The Author(s) 2018.

2. Genetic Architecture of the Inflammatory Bowel Diseases Across East Asian and European Ancestries, Nature Genetics (2023)

3. Analysis of the Genetic Component of Systemic Sclerosis in Iranian and Turkish Populations Through a Genome-Wide Association Study, Rheumatology (United Kingdom) (2019)

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Reza Malekzadeh (2)

Hoda Kavoosi (1)

Style	Citing Format
MLA	Degenhardt F, et al.. "Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles." Human Molecular Genetics, vol. 28, no. 12, 2019, pp. 20782092-.
APA	Degenhardt F, Wendorff M, Wittig M, Ellinghaus E, Datta LW, Schembri J, Ng SC, Rosati E, Hubenthal M, Ellinghaus D, Jung ES, Lieb W, Abedian S, Malekzadeh R, Cheon JH, Ellul P, Sood A, Midha V, Thelma BK, ... Franke A (2019). Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles. Human Molecular Genetics, 28(12), 20782092-.
Chicago	Degenhardt F, Wendorff M, Wittig M, Ellinghaus E, Datta LW, Schembri J, Ng SC, et al.. "Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles." Human Molecular Genetics 28, no. 12 (2019): 20782092-.
Harvard	Degenhardt F et al. (2019) 'Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles', Human Molecular Genetics, 28(12), pp. 20782092-.
Vancouver	Degenhardt F, Wendorff M, Wittig M, Ellinghaus E, Datta LW, Schembri J, et al.. Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles. Human Molecular Genetics. 2019;28(12):20782092-.
BibTex	@article{ author = {Degenhardt F and Wendorff M and Wittig M and Ellinghaus E and Datta LW and Schembri J and Ng SC and Rosati E and Hubenthal M and Ellinghaus D and Jung ES and Lieb W and Abedian S and Malekzadeh R and Cheon JH and Ellul P and Sood A and Midha V and Thelma BK and Wong SH and Schreiber S and Yamazaki K and Kubo M and Boucher G and Rioux JD and Lenz TL and Brant SR and Franke A}, title = {Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles}, journal = {Human Molecular Genetics}, volume = {28}, number = {12}, pages = {20782092-}, year = {2019} }
RIS	TY - JOUR AU - Degenhardt F AU - Wendorff M AU - Wittig M AU - Ellinghaus E AU - Datta LW AU - Schembri J AU - Ng SC AU - Rosati E AU - Hubenthal M AU - Ellinghaus D AU - Jung ES AU - Lieb W AU - Abedian S AU - Malekzadeh R AU - Cheon JH AU - Ellul P AU - Sood A AU - Midha V AU - Thelma BK AU - Wong SH AU - Schreiber S AU - Yamazaki K AU - Kubo M AU - Boucher G AU - Rioux JD AU - Lenz TL AU - Brant SR AU - Franke A TI - Construction and Benchmarking of a Multi-Ethnic Reference Panel for the Imputation of Hla Class I and Ii Alleles JO - Human Molecular Genetics VL - 28 IS - 12 SP - 20782092 EP - PY - 2019 ER -

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