PMID- 30590525
OWN - NLM
STAT- MEDLINE
DCOM- 20200206
LR  - 20221207
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 28
IP  - 12
DP  - 2019 Jun 15
TI  - Construction and benchmarking of a multi-ethnic reference panel for the 
      imputation of HLA class I and II alleles.
PG  - 2078-2092
LID - 10.1093/hmg/ddy443 [doi]
AB  - 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.
CI  - (c) The Author(s) 2018. Published by Oxford University Press.
FAU - Degenhardt, Frauke
AU  - Degenhardt F
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
FAU - Wendorff, Mareike
AU  - Wendorff M
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
FAU - Wittig, Michael
AU  - Wittig M
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
FAU - Ellinghaus, Eva
AU  - Ellinghaus E
AD  - K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, 
      University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
FAU - Datta, Lisa W
AU  - Datta LW
AD  - Department of Medicine, Meyerhoff Inflammatory Bowel Disease Center, Johns 
      Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Schembri, John
AU  - Schembri J
AD  - Division of Gastroenterology, Mater Dei Hospital, Msida MSD, Malta.
FAU - Ng, Siew C
AU  - Ng SC
AD  - Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS 
      Institute of Health Science, State Key Laboratory of Digestive Disease, The 
      Chinese University of Hong Kong, Hong Kong, China.
FAU - Rosati, Elisa
AU  - Rosati E
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
FAU - Hubenthal, Matthias
AU  - Hubenthal M
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
FAU - Ellinghaus, David
AU  - Ellinghaus D
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
FAU - Jung, Eun Suk
AU  - Jung ES
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
AD  - Department of Internal Medicine and Institute of Gastroenterology, Yonsei 
      University College of Medicine, Seoul, Republic of Korea.
FAU - Lieb, Wolfgang
AU  - Lieb W
AD  - Biobank PopGen and Institute of Epidemiology, University Hospital 
      Schleswig-Holstein, Campus Kiel, Kiel, Germany.
FAU - Abedian, Shifteh
AU  - Abedian S
AD  - Department of Epidemiology, University Medical Center Groningen, RB Groningen, 
      The Netherlands.
AD  - Digestive Disease Research Center, Digestive Disease Research Institute, Tehran 
      University of Medical Sciences, Tehran, Iran.
FAU - Malekzadeh, Reza
AU  - Malekzadeh R
AD  - Digestive Disease Research Center, Digestive Disease Research Institute, Tehran 
      University of Medical Sciences, Tehran, Iran.
FAU - Cheon, Jae Hee
AU  - Cheon JH
AD  - Department of Internal Medicine and Institute of Gastroenterology, Yonsei 
      University College of Medicine, Seoul, Republic of Korea.
FAU - Ellul, Pierre
AU  - Ellul P
AD  - Division of Gastroenterology, Mater Dei Hospital, Msida MSD, Malta.
FAU - Sood, Ajit
AU  - Sood A
AD  - Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 
      Punjab, India.
FAU - Midha, Vandana
AU  - Midha V
AD  - Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 
      Punjab, India.
AD  - Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, 
      India.
FAU - Thelma, B K
AU  - Thelma BK
AD  - Department of Genetics, University of Delhi South Campus, New Delhi, India.
FAU - Wong, Sunny H
AU  - Wong SH
AD  - Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS 
      Institute of Health Science, State Key Laboratory of Digestive Disease, The 
      Chinese University of Hong Kong, Hong Kong, China.
FAU - Schreiber, Stefan
AU  - Schreiber S
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
AD  - Department of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
FAU - Yamazaki, Keiko
AU  - Yamazaki K
AD  - Laboratory for Genotyping Development, Center for Integrative Medical Sciences, 
      RIKEN Yokohama Institute, Yokohama, Japan.
AD  - Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research 
      Center, Nihon University School of Medicine, Tokyo, Japan.
FAU - Kubo, Michiaki
AU  - Kubo M
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FAU - Boucher, Gabrielle
AU  - Boucher G
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada.
FAU - Rioux, John D
AU  - Rioux JD
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada.
AD  - Universite de Montreal Department of Medicine, Montreal, Quebec, Canada.
FAU - Lenz, Tobias L
AU  - Lenz TL
AD  - Research Group for Evolutionary Immunogenomics, Max Planck Institute for 
      Evolutionary Biology, Plon, Germany.
FAU - Brant, Steven R
AU  - Brant SR
AD  - Department of Medicine, Meyerhoff Inflammatory Bowel Disease Center, Johns 
      Hopkins University School of Medicine, Baltimore, MD, USA.
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, MD, USA.
AD  - Department of Medicine, Rutgers Robert Wood Johnson Medical School and Department 
      of Genetics, Rutgers University, New Brunswick and Piscataway, NJ, USA.
FAU - Franke, Andre
AU  - Franke A
AD  - Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 
      Kiel, Germany.
LA  - eng
GR  - U01 DK062432/DK/NIDDK NIH HHS/United States
GR  - U01 DK062422/DK/NIDDK NIH HHS/United States
GR  - U01 DK062423/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420/DK/NIDDK NIH HHS/United States
GR  - U01 DK062431/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DRB3 Chains)
RN  - 0 (HLA-DRB4 Chains)
RN  - 0 (HLA-DRB5 Chains)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Black or African American/ethnology/genetics
MH  - Alleles
MH  - Asian People
MH  - Benchmarking
MH  - Cluster Analysis
MH  - Ethnicity
MH  - Gene Frequency
MH  - Genotype
MH  - HLA Antigens/genetics
MH  - HLA-DRB3 Chains/genetics
MH  - HLA-DRB4 Chains/genetics
MH  - HLA-DRB5 Chains/genetics
MH  - Haplotypes
MH  - High-Throughput Nucleotide Sequencing
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - Retrospective Studies
MH  - White People/ethnology/genetics
PMC - PMC6548229
EDAT- 2018/12/28 06:00
MHDA- 2020/02/07 06:00
PMCR- 2018/12/26
CRDT- 2018/12/28 06:00
PHST- 2018/08/09 00:00 [received]
PHST- 2018/12/17 00:00 [revised]
PHST- 2018/12/18 00:00 [accepted]
PHST- 2018/12/28 06:00 [pubmed]
PHST- 2020/02/07 06:00 [medline]
PHST- 2018/12/28 06:00 [entrez]
PHST- 2018/12/26 00:00 [pmc-release]
AID - 5261434 [pii]
AID - ddy443 [pii]
AID - 10.1093/hmg/ddy443 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2019 Jun 15;28(12):2078-2092. doi: 10.1093/hmg/ddy443.