PMID- 37495751
OWN - NLM
STAT- MEDLINE
DCOM- 20230908
LR  - 20240301
IS  - 1750-2799 (Electronic)
IS  - 1754-2189 (Print)
IS  - 1750-2799 (Linking)
VI  - 18
IP  - 9
DP  - 2023 Sep
TI  - Tutorial: a statistical genetics guide to identifying HLA alleles driving complex 
      disease.
PG  - 2625-2641
LID - 10.1038/s41596-023-00853-4 [doi]
AB  - The human leukocyte antigen (HLA) locus is associated with more complex diseases 
      than any other locus in the human genome. In many diseases, HLA explains more 
      heritability than all other known loci combined. In silico HLA imputation methods 
      enable rapid and accurate estimation of HLA alleles in the millions of 
      individuals that are already genotyped on microarrays. HLA imputation has been 
      used to define causal variation in autoimmune diseases, such as type I diabetes, 
      and in human immunodeficiency virus infection control. However, there are few 
      guidelines on performing HLA imputation, association testing, and fine mapping. 
      Here, we present a comprehensive tutorial to impute HLA alleles from genotype 
      data. We provide detailed guidance on performing standard quality control 
      measures for input genotyping data and describe options to impute HLA alleles and 
      amino acids either locally or using the web-based Michigan Imputation Server, 
      which hosts a multi-ancestry HLA imputation reference panel. We also offer best 
      practice recommendations to conduct association tests to define the alleles, 
      amino acids, and haplotypes that affect human traits. Along with the pipeline, we 
      provide a step-by-step online guide with scripts and available software ( 
      https://github.com/immunogenomics/HLA_analyses_tutorial ). This tutorial will be 
      broadly applicable to large-scale genotyping data and will contribute to defining 
      the role of HLA in human diseases across global populations.
CI  - (c) 2023. Springer Nature Limited.
FAU - Sakaue, Saori
AU  - Sakaue S
AUID- ORCID: 0000-0003-3618-9717
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
FAU - Gurajala, Saisriram
AU  - Gurajala S
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
FAU - Curtis, Michelle
AU  - Curtis M
AUID- ORCID: 0000-0002-6843-4839
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
FAU - Luo, Yang
AU  - Luo Y
AUID- ORCID: 0000-0001-7385-6166
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
AD  - Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
FAU - Choi, Wanson
AU  - Choi W
AUID- ORCID: 0000-0003-1251-8213
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, South Korea.
FAU - Ishigaki, Kazuyoshi
AU  - Ishigaki K
AUID- ORCID: 0000-0003-2881-0657
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
AD  - Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Kang, Joyce B
AU  - Kang JB
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
FAU - Rumker, Laurie
AU  - Rumker L
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
FAU - Deutsch, Aaron J
AU  - Deutsch AJ
AUID- ORCID: 0000-0001-6750-5335
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
AD  - Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston, 
      MA, USA.
AD  - Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical 
      School, Boston, MA, USA.
AD  - Program in Metabolism, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Schonherr, Sebastian
AU  - Schonherr S
AD  - Institute of Genetic Epidemiology, Department of Genetics, Medical University of 
      Innsbruck, Innsbruck, Austria.
FAU - Forer, Lukas
AU  - Forer L
AD  - Institute of Genetic Epidemiology, Department of Genetics, Medical University of 
      Innsbruck, Innsbruck, Austria.
FAU - LeFaive, Jonathon
AU  - LeFaive J
AUID- ORCID: 0000-0003-3668-6086
AD  - Center for Statistical Genetics, University of Michigan School of Public Health, 
      Ann Arbor, MI, USA.
AD  - Department of Biostatistics, University of Michigan School of Public Health, Ann 
      Arbor, MI, USA.
FAU - Fuchsberger, Christian
AU  - Fuchsberger C
AD  - Institute of Genetic Epidemiology, Department of Genetics, Medical University of 
      Innsbruck, Innsbruck, Austria.
AD  - Center for Statistical Genetics, University of Michigan School of Public Health, 
      Ann Arbor, MI, USA.
AD  - Department of Biostatistics, University of Michigan School of Public Health, Ann 
      Arbor, MI, USA.
AD  - Institute for Biomedicine, Eurac Research, Bolzano, Italy.
FAU - Han, Buhm
AU  - Han B
AD  - Department of Biomedical Sciences, Seoul National University College of Medicine, 
      Seoul, South Korea.
AD  - Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, 
      South Korea.
FAU - Lenz, Tobias L
AU  - Lenz TL
AD  - Research Unit for Evolutionary Immunogenomics, Department of Biology, University 
      of Hamburg, Hamburg, Germany.
FAU - de Bakker, Paul I W
AU  - de Bakker PIW
AD  - Data and Computational Sciences, Vertex Pharmaceuticals, Boston, MA, USA.
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.
AD  - Integrated Frontier Research for Medical Science Division, Institute for Open and 
      Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.
AD  - Laboratory of Statistical Immunology, Immunology Frontier Research Center 
      (WPI-IFReC), Osaka University, Suita, Japan.
AD  - Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, 
      Yokohama, Japan.
AD  - Center for Infectious Disease Education and Research (CiDER), Osaka University, 
      Suita, Japan.
AD  - Department of Genome Informatics, Graduate School of Medicine, The University of 
      Tokyo, Tokyo, Japan.
FAU - Smith, Albert V
AU  - Smith AV
AD  - Center for Statistical Genetics, University of Michigan School of Public Health, 
      Ann Arbor, MI, USA.
AD  - Department of Biostatistics, University of Michigan School of Public Health, Ann 
      Arbor, MI, USA.
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
AUID- ORCID: 0000-0002-1901-8265
AD  - Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA. soumya@broadinstitute.org.
AD  - Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and 
      Women's Hospital, Harvard Medical School, Boston, MA, USA. 
      soumya@broadinstitute.org.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA. soumya@broadinstitute.org.
AD  - Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 
      soumya@broadinstitute.org.
AD  - Centre for Genetics and Genomics Versus Arthritis, University of Manchester, 
      Manchester, UK. soumya@broadinstitute.org.
LA  - eng
GR  - T32 DK007028/DK/NIDDK NIH HHS/United States
GR  - UC2 AR081023/AR/NIAMS NIH HHS/United States
GR  - T32 GM007753/GM/NIGMS NIH HHS/United States
GR  - T32 GM144273/GM/NIGMS NIH HHS/United States
GR  - R01 AR063759/AR/NIAMS NIH HHS/United States
GR  - U01 HG009379/HG/NHGRI NIH HHS/United States
GR  - U01 HG012009/HG/NHGRI NIH HHS/United States
GR  - F30 AI172238/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230726
PL  - England
TA  - Nat Protoc
JT  - Nature protocols
JID - 101284307
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Amino Acids)
SB  - IM
MH  - Humans
MH  - Alleles
MH  - *HLA Antigens/genetics
MH  - Genotype
MH  - *Histocompatibility Antigens Class I
MH  - Haplotypes
MH  - Amino Acids/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Genome-Wide Association Study
PMC - PMC10786448
MID - NIHMS1954702
EDAT- 2023/07/27 01:09
MHDA- 2023/09/08 06:43
PMCR- 2024/01/12
CRDT- 2023/07/26 23:27
PHST- 2022/08/10 00:00 [received]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/09/08 06:43 [medline]
PHST- 2023/07/27 01:09 [pubmed]
PHST- 2023/07/26 23:27 [entrez]
PHST- 2024/01/12 00:00 [pmc-release]
AID - 10.1038/s41596-023-00853-4 [pii]
AID - 10.1038/s41596-023-00853-4 [doi]
PST - ppublish
SO  - Nat Protoc. 2023 Sep;18(9):2625-2641. doi: 10.1038/s41596-023-00853-4. Epub 2023 
      Jul 26.