PMID- 33712626
OWN - NLM
STAT- MEDLINE
DCOM- 20210401
LR  - 20230129
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Mar 12
TI  - A deep learning method for HLA imputation and trans-ethnic MHC fine-mapping of 
      type 1 diabetes.
PG  - 1639
LID - 10.1038/s41467-021-21975-x [doi]
LID - 1639
AB  - Conventional human leukocyte antigen (HLA) imputation methods drop their 
      performance for infrequent alleles, which is one of the factors that reduce the 
      reliability of trans-ethnic major histocompatibility complex (MHC) fine-mapping 
      due to inter-ethnic heterogeneity in allele frequency spectra. We develop 
      DEEP*HLA, a deep learning method for imputing HLA genotypes. Through validation 
      using the Japanese and European HLA reference panels (n = 1,118 and 5,122), 
      DEEP*HLA achieves the highest accuracies with significant superiority for 
      low-frequency and rare alleles. DEEP*HLA is less dependent on distance-dependent 
      linkage disequilibrium decay of the target alleles and might capture the 
      complicated region-wide information. We apply DEEP*HLA to type 1 diabetes GWAS 
      data from BioBank Japan (n = 62,387) and UK Biobank (n = 354,459), and 
      successfully disentangle independently associated class I and II HLA variants 
      with shared risk among diverse populations (the top signal at amino acid position 
      71 of HLA-DRbeta1; P = 7.5 x 10(-120)). Our study illustrates the value of deep 
      learning in genotype imputation and trans-ethnic MHC fine-mapping.
FAU - Naito, Tatsuhiko
AU  - Naito T
AUID- ORCID: 0000-0002-2779-4600
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      Suita, Japan.
AD  - Department of Neurology, Graduate School of Medicine, The University of Tokyo, 
      Tokyo, Japan.
FAU - Suzuki, Ken
AU  - Suzuki K
AUID- ORCID: 0000-0003-1065-3593
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      Suita, Japan.
FAU - Hirata, Jun
AU  - Hirata J
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      Suita, Japan.
AD  - Pharmaceutical Discovery Research Laboratories, Teijin Pharma Limited, Hino, 
      Japan.
FAU - Kamatani, Yoichiro
AU  - Kamatani Y
AD  - Laboratory of Complex Trait Genomics, Department of Computational Biology and 
      Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 
      Tokyo, Japan.
FAU - Matsuda, Koichi
AU  - Matsuda K
AUID- ORCID: 0000-0001-7292-2686
AD  - Laboratory of Clinical Genome Sequencing, Department of Computational Biology and 
      Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 
      Tokyo, Japan.
FAU - Toda, Tatsushi
AU  - Toda T
AD  - Department of Neurology, Graduate School of Medicine, The University of Tokyo, 
      Tokyo, Japan.
FAU - Okada, Yukinori
AU  - Okada Y
AUID- ORCID: 0000-0002-0311-8472
AD  - Department of Statistical Genetics, Osaka University Graduate School of Medicine, 
      Suita, Japan. yokada@sg.med.osaka-u.ac.jp.
AD  - Laboratory of Statistical Immunology, Immunology Frontier Research Center 
      (WPI-IFReC), Osaka University, Suita, Japan. yokada@sg.med.osaka-u.ac.jp.
AD  - Integrated Frontier Research for Medical Science Division, Institute for Open and 
      Transdisciplinary Research Initiatives, Osaka University, Suita, Japan. 
      yokada@sg.med.osaka-u.ac.jp.
LA  - eng
GR  - MC_PC_17228/MRC_/Medical Research Council/United Kingdom
GR  - MC_QA137853/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210312
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Alleles
MH  - *Deep Learning
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Ethnicity/genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Histocompatibility Antigens Class I/genetics
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Major Histocompatibility Complex/*genetics
MH  - Racial Groups
PMC - PMC7955122
COIS- The authors declare no competing interests.
EDAT- 2021/03/14 06:00
MHDA- 2021/04/02 06:00
PMCR- 2021/03/12
CRDT- 2021/03/13 06:00
PHST- 2020/11/24 00:00 [received]
PHST- 2021/02/19 00:00 [accepted]
PHST- 2021/03/13 06:00 [entrez]
PHST- 2021/03/14 06:00 [pubmed]
PHST- 2021/04/02 06:00 [medline]
PHST- 2021/03/12 00:00 [pmc-release]
AID - 10.1038/s41467-021-21975-x [pii]
AID - 21975 [pii]
AID - 10.1038/s41467-021-21975-x [doi]
PST - epublish
SO  - Nat Commun. 2021 Mar 12;12(1):1639. doi: 10.1038/s41467-021-21975-x.