PMID- 38375425
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240417
IS  - 2312-0541 (Print)
IS  - 2312-0541 (Electronic)
IS  - 2312-0541 (Linking)
VI  - 10
IP  - 1
DP  - 2024 Jan
TI  - Association study of human leukocyte antigen variants and idiopathic pulmonary 
      fibrosis.
LID - 00553-2023 [pii]
LID - 10.1183/23120541.00553-2023 [doi]
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial 
      pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent 
      studies have highlighted the potential role of infection in the pathogenesis of 
      IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic 
      interstitial pneumonia (including IPF) has been reported. Owing to the important 
      role that the human leukocyte antigen (HLA) region plays in the immune response, 
      here we evaluated if HLA genetic variation was associated specifically with IPF 
      risk. METHODS: We performed a meta-analysis of associations of the HLA region 
      with IPF risk in individuals of European ancestry from seven independent 
      case-control studies of IPF (comprising 5159 cases and 27 459 controls, including 
      a prior study of fibrotic interstitial pneumonia). Single nucleotide 
      polymorphisms, classical HLA alleles and amino acids were analysed and signals 
      meeting a region-wide association threshold of p<4.5x10(-4) and a posterior 
      probability of replication >90% were considered significant. We sought to 
      replicate the previously reported HLA-DQB1 association in the subset of studies 
      independent of the original report. RESULTS: The meta-analysis of all seven 
      studies identified four significant independent single nucleotide polymorphisms 
      associated with IPF risk. However, none met the posterior probability for 
      replication criterion. The HLA-DQB1 association was not replicated in the 
      independent IPF studies. CONCLUSION: Variation in the HLA region was not 
      consistently associated with risk in studies of IPF. However, this does not 
      preclude the possibility that other genomic regions linked to the immune response 
      may be involved in the aetiology of IPF.
CI  - Copyright (c)The authors 2024.
FAU - Guillen-Guio, Beatriz
AU  - Guillen-Guio B
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
AD  - Joint first authors.
FAU - Paynton, Megan L
AU  - Paynton ML
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - Joint first authors.
FAU - Allen, Richard J
AU  - Allen RJ
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Chin, Daniel P W
AU  - Chin DPW
AUID- ORCID: 0000-0002-7349-895X
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Donoghue, Lauren J
AU  - Donoghue LJ
AD  - Genentech, San Francisco, CA, USA.
FAU - Stockwell, Amy
AU  - Stockwell A
AD  - Genentech, San Francisco, CA, USA.
FAU - Leavy, Olivia C
AU  - Leavy OC
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Hernandez-Beeftink, Tamara
AU  - Hernandez-Beeftink T
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Reynolds, Carl
AU  - Reynolds C
AUID- ORCID: 0000-0002-7415-258X
AD  - National Heart & Lung Institute, Imperial College London, London, UK.
FAU - Cullinan, Paul
AU  - Cullinan P
AD  - National Heart & Lung Institute, Imperial College London, London, UK.
FAU - Martinez, Fernando
AU  - Martinez F
AD  - Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
FAU - Booth, Helen L
AU  - Booth HL
AD  - University College Hospital, University College London, London, UK.
FAU - Fahy, William A
AU  - Fahy WA
AD  - GlaxoSmithKline, London, UK.
FAU - Hall, Ian P
AU  - Hall IP
AD  - School of Medicine, University of Nottingham, Nottingham, UK.
AD  - National Institute for Health Research, Nottingham Biomedical Research Centre, 
      Nottingham, UK.
FAU - Hart, Simon P
AU  - Hart SP
AUID- ORCID: 0000-0003-4606-9559
AD  - Hull York Medical School, University of Hull, Hull, UK.
FAU - Hill, Mike R
AU  - Hill MR
AD  - MRC Population Health Unit, University of Oxford, Oxford, UK.
FAU - Hirani, Nik
AU  - Hirani N
AD  - Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
FAU - Hubbard, Richard B
AU  - Hubbard RB
AD  - School of Medicine, University of Nottingham, Nottingham, UK.
AD  - National Institute for Health Research, Nottingham Biomedical Research Centre, 
      Nottingham, UK.
FAU - McAnulty, Robin J
AU  - McAnulty RJ
AD  - Division of Medicine, University College London, London, UK.
FAU - Millar, Ann B
AU  - Millar AB
AD  - Bristol Medical School, University of Bristol, Bristol, UK.
FAU - Navaratnam, Vidya
AU  - Navaratnam V
AD  - Division of Epidemiology and Public Health, University of Nottingham, Nottingham, 
      UK.
AD  - National Institute for Health Research, Nottingham Biomedical Research Centre, 
      Nottingham University Hospitals NHS Trust, Nottingham, UK.
AD  - Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, QLD, 
      Australia.
FAU - Oballa, Eunice
AU  - Oballa E
AD  - GlaxoSmithKline, London, UK.
FAU - Parfrey, Helen
AU  - Parfrey H
AUID- ORCID: 0000-0002-4515-5634
AD  - Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.
FAU - Saini, Gauri
AU  - Saini G
AD  - School of Medicine, University of Nottingham, Nottingham, UK.
FAU - Sayers, Ian
AU  - Sayers I
AD  - Centre for Respiratory Research, NIHR Nottingham Biomedical Research Centre, 
      School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, 
      UK.
FAU - Tobin, Martin D
AU  - Tobin MD
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Whyte, Moira K B
AU  - Whyte MKB
AD  - Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
FAU - Adegunsoye, Ayodeji
AU  - Adegunsoye A
AD  - Department of Medicine, University of Chicago, Chicago, IL, USA.
FAU - Kaminski, Naftali
AU  - Kaminski N
AUID- ORCID: 0000-0001-5917-4601
AD  - Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, 
      CT, USA.
FAU - Ma, Shwu-Fan
AU  - Ma SF
AD  - Department of Medicine, University of Virginia, Charlottesville, VA, USA.
FAU - Strek, Mary E
AU  - Strek ME
AD  - Department of Medicine, University of Chicago, Chicago, IL, USA.
FAU - Zhang, Yingze
AU  - Zhang Y
AUID- ORCID: 0000-0001-6947-2901
AD  - Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of 
      Pittsburgh, Pittsburgh, PA, USA.
FAU - Fingerlin, Tasha E
AU  - Fingerlin TE
AD  - Department of Immunology and Genomic Medicine, National Jewish Health, Denver, 
      CO, USA.
FAU - Molina-Molina, Maria
AU  - Molina-Molina M
AD  - Servei de Pneumologia, Laboratori de Pneumologia Experimental, Instituto de 
      Investigacion Biomedica de Bellvitge (IDIBELL), Barcelona, Spain.
AD  - Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), 
      Instituto de Salud Carlos III, Madrid, Spain.
FAU - Neighbors, Margaret
AU  - Neighbors M
AD  - Genentech, San Francisco, CA, USA.
FAU - Sheng, X Rebecca
AU  - Sheng XR
AD  - Genentech, San Francisco, CA, USA.
FAU - Oldham, Justin M
AU  - Oldham JM
AD  - Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Maher, Toby M
AU  - Maher TM
AD  - National Heart and Lung Institute, Imperial College London, London, UK.
AD  - Division of Pulmonary and Critical Care Medicine, University of Southern 
      California, Los Angeles, USA.
FAU - Molyneaux, Philip L
AU  - Molyneaux PL
AUID- ORCID: 0000-0003-1301-8800
AD  - National Heart and Lung Institute, Imperial College London, London, UK.
AD  - Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation 
      Trust, London, UK.
FAU - Flores, Carlos
AU  - Flores C
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), 
      Instituto de Salud Carlos III, Madrid, Spain.
AD  - Research Unit, Hospital Universitario Nuestra Senora de Candelaria, Santa Cruz de 
      Tenerife, Spain.
AD  - Genomics Division, Instituto Tecnologico y de Energias Renovables, Santa Cruz de 
      Tenerife, Spain.
AD  - Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las 
      Palmas de Gran Canaria, Spain.
FAU - Noth, Imre
AU  - Noth I
AD  - Department of Medicine, University of Virginia, Charlottesville, VA, USA.
FAU - Schwartz, David A
AU  - Schwartz DA
AD  - Department of Medicine, University of Colorado, Anscuhtz, CO, USA.
FAU - Yaspan, Brian L
AU  - Yaspan BL
AUID- ORCID: 0000-0002-3787-2510
AD  - Genentech, San Francisco, CA, USA.
FAU - Jenkins, R Gisli
AU  - Jenkins RG
AD  - National Heart and Lung Institute, Imperial College London, London, UK.
FAU - Wain, Louise V
AU  - Wain LV
AD  - Department of Population Health Sciences, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
AD  - Joint senior authors.
FAU - Hollox, Edward J
AU  - Hollox EJ
AUID- ORCID: 0000-0002-0115-2298
AD  - Department of Genetics and Genome Biology, University of Leicester, Leicester, 
      UK.
AD  - Joint senior authors.
LA  - eng
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - R56 HL158935/HL/NHLBI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - CDA 13-017/HX/HSRD VA/United States
GR  - R01 HL169166/HL/NHLBI NIH HHS/United States
GR  - P01 HL162607/HL/NHLBI NIH HHS/United States
GR  - K23 HL138190/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20240219
PL  - England
TA  - ERJ Open Res
JT  - ERJ open research
JID - 101671641
UOF - medRxiv. 2023 Jul 24;:. PMID: 37546732
PMC - PMC10875457
COIS- Conflict of interest: L.J. Donoghue, A. Stockwell, M. Neighbours, X.R. Sheng and 
      B.L. Yaspan are full-time employees of Genentech; A. Stockwell, M. Neighbours, 
      X.R. Sheng and B.L. Yaspan hold stock options in Roche. J.M. Oldham reports 
      personal fees from Boehringer Ingelheim, Genentech, United Therapeutics, AmMax 
      Bio and Lupin Pharmaceuticals outside the submitted work. D.A. Schwartz is the 
      founder and chief scientific officer of Eleven P15, a company focused on the 
      early detection and treatment of pulmonary fibrosis. R.G. Jenkins reports 
      honoraria from Chiesi, Roche, PatientMPower, AstraZeneca, GlaxoSmithKline and 
      Boehringer Ingelheim, and consulting fees from Bristol Myers Squibb, Daewoong, 
      Veracyte, Resolution Therapeutics, RedX, Pliant and Chiesi. L.V. Wain reports 
      research funding from GlaxoSmithKline, Roche and Orion Pharma, and consultancy 
      for GlaxoSmithKline and Galapagos, outside of the submitted work. S.P. Hart and 
      P.L. Molyneaux are associate editors of this journal. The other authors declare 
      no competing interests.
EDAT- 2024/02/20 11:50
MHDA- 2024/02/20 11:51
PMCR- 2024/02/19
CRDT- 2024/02/20 03:45
PHST- 2023/08/01 00:00 [received]
PHST- 2023/11/05 00:00 [accepted]
PHST- 2024/02/20 11:51 [medline]
PHST- 2024/02/20 11:50 [pubmed]
PHST- 2024/02/20 03:45 [entrez]
PHST- 2024/02/19 00:00 [pmc-release]
AID - 00553-2023 [pii]
AID - 10.1183/23120541.00553-2023 [doi]
PST - epublish
SO  - ERJ Open Res. 2024 Feb 19;10(1):00553-2023. doi: 10.1183/23120541.00553-2023. 
      eCollection 2024 Jan.