PMID- 37415598
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 14
DP  - 2023
TI  - Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants 
      associated with late-onset asthma.
PG  - 1173676
LID - 10.3389/fgene.2023.1173676 [doi]
LID - 1173676
AB  - Introduction: Asthma is a chronic disease of the airways that impairs normal 
      breathing. The etiology of asthma is complex and involves multiple factors, 
      including the environment and genetics, especially the distinct genetic 
      architecture associated with ancestry. Compared to early-onset asthma, little is 
      known about genetic predisposition to late-onset asthma. We investigated the 
      race/ethnicity-specific relationship among genetic variants within the major 
      histocompatibility complex (MHC) region and late-onset asthma in a North 
      Carolina-based multiracial cohort of adults. Methods: We stratified all analyses 
      by self-reported race (i.e., White and Black) and adjusted all regression models 
      for age, sex, and ancestry. We conducted association tests within the MHC region 
      and performed fine-mapping analyses conditioned on the race/ethnicity-specific 
      lead variant using whole-genome sequencing (WGS) data. We applied computational 
      methods to infer human leukocyte antigen (HLA) alleles and residues at amino acid 
      positions. We replicated findings in the UK Biobank. Results: The lead signals, 
      rs9265901 on the 5' end of HLA-B, rs55888430 on HLA-DOB, and rs117953947 on 
      HCG17, were significantly associated with late-onset asthma in all, White, and 
      Black participants, respectively (OR = 1.73, 95%CI: 1.31 to 2.14, p = 3.62 x 
      10(-5); OR = 3.05, 95%CI: 1.86 to 4.98, p = 8.85 x 10(-6); OR = 19.5, 95%CI: 4.37 
      to 87.2, p = 9.97 x 10(-5), respectively). For the HLA analysis, HLA-B*40:02 and 
      HLA-DRB1*04:05, HLA-B*40:02, HLA-C*04:01, and HLA-DRB1*04:05, and HLA-DRB1*03:01 
      and HLA-DQB1 were significantly associated with late-onset asthma in all, White, 
      and Black participants. Conclusion: Multiple genetic variants within the MHC 
      region were significantly associated with late-onset asthma, and the associations 
      were significantly different by race/ethnicity group.
CI  - Copyright (c) 2023 Lee, Choi, Burkholder, Perera, Mack, Miller, Fessler, Cook, 
      Karmaus, Nakano, Garantziotis, Madenspacher, House, Akhtari, Schmitt, Fargo, Hall 
      and Motsinger-Reif.
FAU - Lee, Eunice Y
AU  - Lee EY
AD  - Biostatistics and Computational Biology Branch, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Choi, Wonson
AU  - Choi W
AD  - Genomics and Bioinformatics Laboratory, Seoul National University, Seoul, 
      Republic of Korea.
FAU - Burkholder, Adam B
AU  - Burkholder AB
AD  - National Institute of Environmental Health Sciences, Durham, NC, United States.
FAU - Perera, Lalith
AU  - Perera L
AD  - Genomic Integrity and Structural Biology Laboratory, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Mack, Jasmine A
AU  - Mack JA
AD  - Biostatistics and Computational Biology Branch, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
AD  - Department of Obstetrics and Gynecology, University of Cambridge, Cambridge, 
      United Kingdom.
FAU - Miller, Frederick W
AU  - Miller FW
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Fessler, Michael B
AU  - Fessler MB
AD  - Immunity, Inflammation and Disease Laboratory, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Cook, Donald N
AU  - Cook DN
AD  - Immunity, Inflammation and Disease Laboratory, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
AD  - Immunogenetics Group, National Institute of Environmental Health Sciences, 
      Durham, NC, United States.
FAU - Karmaus, Peer W F
AU  - Karmaus PWF
AD  - Immunity, Inflammation and Disease Laboratory, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Nakano, Hideki
AU  - Nakano H
AD  - Immunity, Inflammation and Disease Laboratory, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Garantziotis, Stavros
AU  - Garantziotis S
AD  - Clinical Research Branch, National Institute of Environmental Health Sciences, 
      Durham, NC, United States.
FAU - Madenspacher, Jennifer H
AU  - Madenspacher JH
AD  - Clinical Research Branch, National Institute of Environmental Health Sciences, 
      Durham, NC, United States.
FAU - House, John S
AU  - House JS
AD  - Biostatistics and Computational Biology Branch, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
FAU - Akhtari, Farida S
AU  - Akhtari FS
AD  - Biostatistics and Computational Biology Branch, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
AD  - Clinical Research Branch, National Institute of Environmental Health Sciences, 
      Durham, NC, United States.
FAU - Schmitt, Charles S
AU  - Schmitt CS
AD  - Division of Translational Toxicology, National Institute of Environmental Health 
      Sciences, Durham, NC, United States.
FAU - Fargo, David C
AU  - Fargo DC
AD  - National Institute of Environmental Health Sciences, Durham, NC, United States.
FAU - Hall, Janet E
AU  - Hall JE
AD  - Clinical Research Branch, National Institute of Environmental Health Sciences, 
      Durham, NC, United States.
FAU - Motsinger-Reif, Alison A
AU  - Motsinger-Reif AA
AD  - Biostatistics and Computational Biology Branch, National Institute of 
      Environmental Health Sciences, Durham, NC, United States.
LA  - eng
PT  - Journal Article
DEP - 20230621
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC10321602
OTO - NOTNLM
OT  - HLA allele
OT  - MHC
OT  - ethnicity
OT  - immune function
OT  - late-onset asthma
OT  - race
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/07/07 06:42
MHDA- 2023/07/07 06:43
PMCR- 2023/06/21
CRDT- 2023/07/07 03:54
PHST- 2023/02/24 00:00 [received]
PHST- 2023/06/09 00:00 [accepted]
PHST- 2023/07/07 06:43 [medline]
PHST- 2023/07/07 06:42 [pubmed]
PHST- 2023/07/07 03:54 [entrez]
PHST- 2023/06/21 00:00 [pmc-release]
AID - 1173676 [pii]
AID - 10.3389/fgene.2023.1173676 [doi]
PST - epublish
SO  - Front Genet. 2023 Jun 21;14:1173676. doi: 10.3389/fgene.2023.1173676. eCollection 
      2023.