دورية أكاديمية
Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants associated with late-onset asthma.
| العنوان: | Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants associated with late-onset asthma. |
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| المؤلفون: | Lee EY; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., Choi W; Genomics and Bioinformatics Laboratory, Seoul National University, Seoul, Republic of Korea., Burkholder AB; National Institute of Environmental Health Sciences, Durham, NC, United States., Perera L; Genomic Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United States., Mack JA; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, NC, United States.; Department of Obstetrics and Gynecology, University of Cambridge, Cambridge, United Kingdom., Miller FW; Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., Fessler MB; Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United States., Cook DN; Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United States.; Immunogenetics Group, National Institute of Environmental Health Sciences, Durham, NC, United States., Karmaus PWF; Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United States., Nakano H; Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United States., Garantziotis S; Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., Madenspacher JH; Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., House JS; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., Akhtari FS; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, NC, United States.; Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., Schmitt CS; Division of Translational Toxicology, National Institute of Environmental Health Sciences, Durham, NC, United States., Fargo DC; National Institute of Environmental Health Sciences, Durham, NC, United States., Hall JE; Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, NC, United States., Motsinger-Reif AA; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, NC, United States. |
| المصدر: | Frontiers in genetics [Front Genet] 2023 Jun 21; Vol. 14, pp. 1173676. Date of Electronic Publication: 2023 Jun 21 (Print Publication: 2023). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101560621 Publication Model: eCollection Cited Medium: Print ISSN: 1664-8021 (Print) Linking ISSN: 16648021 NLM ISO Abbreviation: Front Genet Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Research Foundation. |
| مستخلص: | 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 × 10 -5 ; OR = 3.05, 95%CI: 1.86 to 4.98, p = 8.85 × 10 -6 ; OR = 19.5, 95%CI: 4.37 to 87.2, p = 9.97 × 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. Competing Interests: 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. (Copyright © 2023 Lee, Choi, Burkholder, Perera, Mack, Miller, Fessler, Cook, Karmaus, Nakano, Garantziotis, Madenspacher, House, Akhtari, Schmitt, Fargo, Hall and Motsinger-Reif.) |
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| فهرسة مساهمة: | Keywords: HLA allele; MHC; ethnicity; immune function; late-onset asthma; race |
| تواريخ الأحداث: | Date Created: 20230707 Latest Revision: 20230718 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10321602 |
| DOI: | 10.3389/fgene.2023.1173676 |
| PMID: | 37415598 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-8021 |
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| DOI: | 10.3389/fgene.2023.1173676 |