PMID- 37546732
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240313
DP  - 2023 Jul 24
TI  - Association study of human leukocyte antigen (HLA) variants and idiopathic 
      pulmonary fibrosis.
LID - 2023.07.20.23292940 [pii]
LID - 10.1101/2023.07.20.23292940 [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. Due 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 a total of 5,159 cases and 27,459 
      controls, including the 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 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.
FAU - Guillen-Guio, Beatriz
AU  - Guillen-Guio B
AD  - Department of Population Health Sciences, University of Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Paynton, Megan L
AU  - Paynton ML
AD  - Department of Population Health Sciences, University of Leicester, UK.
FAU - Allen, Richard J
AU  - Allen RJ
AD  - Department of Population Health Sciences, University of Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Chin, Daniel P W
AU  - Chin DPW
AD  - Department of Population Health Sciences, University of Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Donoghue, Lauren J
AU  - Donoghue LJ
AD  - Genentech, California, USA.
FAU - Stockwell, Amy
AU  - Stockwell A
AD  - Genentech, California, USA.
FAU - Leavy, Olivia C
AU  - Leavy OC
AD  - Department of Population Health Sciences, University of 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, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Reynolds, Carl
AU  - Reynolds C
AD  - Imperial College London, London, UK.
FAU - Cullinan, Paul
AU  - Cullinan P
AD  - Imperial College London, London, UK.
FAU - Martinez, Fernando
AU  - Martinez F
AD  - Weill Cornell Medicine, New York, USA.
CN  - CleanUP-IPF Investigators of the Pulmonary Trials Cooperative
FAU - Booth, Helen L
AU  - Booth HL
AD  - University College London Hospitals, London, UK.
FAU - Fahy, William A
AU  - Fahy WA
AD  - GlaxoSmithKline, London, UK.
FAU - Hall, Ian P
AU  - Hall IP
AD  - University of Nottingham, Nottingham, UK.
AD  - National Institute for Health Research, Nottingham Biomedical Research Centre, 
      Nottingham, UK.
FAU - Hart, Simon P
AU  - Hart SP
AD  - University of Hull, Hull, UK.
FAU - Hill, Mike R
AU  - Hill MR
AD  - University of Oxford, Oxford, UK.
FAU - Hirani, Nik
AU  - Hirani N
AD  - University of Edinburgh, Edinburgh, UK.
FAU - Hubbard, Richard B
AU  - Hubbard RB
AD  - 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  - University College London, London, UK.
FAU - Millar, Ann B
AU  - Millar AB
AD  - 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
AD  - Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.
FAU - Saini, Gauri
AU  - Saini G
AD  - 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, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Whyte, Moira K B
AU  - Whyte MKB
AD  - University of Edinburgh, Edinburgh, UK.
FAU - Adegunsoye, Ayodeji
AU  - Adegunsoye A
AD  - University of Chicago, Chicago, USA.
FAU - Kaminski, Naftali
AU  - Kaminski N
AD  - Yale School of Medicine, Connecticut, USA.
FAU - Shwu-Fan, Ma
AU  - Shwu-Fan M
AD  - University of Virginia, Virginia, USA.
FAU - Strek, Mary E
AU  - Strek ME
AD  - University of Chicago, Chicago, USA.
FAU - Zhang, Yingze
AU  - Zhang Y
AD  - University of Pittsburgh, Pittsburgh, USA.
FAU - Fingerlin, Tasha E
AU  - Fingerlin TE
AD  - National Jewish Health, Colorado, 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, California, USA.
FAU - Sheng, X Rebecca
AU  - Sheng XR
AD  - Genentech, California, USA.
FAU - Oldham, Justin M
AU  - Oldham JM
AD  - University of Michigan, Michigan, 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
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  - University of Virginia, Virginia, USA.
FAU - Schwartz, David A
AU  - Schwartz DA
AD  - University of Colorado Medicine, Colorado, USA.
FAU - Yaspan, Brian L
AU  - Yaspan BL
AD  - Genentech, California, 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, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Hollox, Edward J
AU  - Hollox EJ
AD  - Department of Genetics and Genome Biology, University of Leicester, UK.
LA  - eng
GR  - MC_PC_19004/MRC_/Medical Research Council/United Kingdom
GR  - K23 HL146942/HL/NHLBI NIH HHS/United States
GR  - R56 HL158935/HL/NHLBI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - K23 HL138190/HL/NHLBI NIH HHS/United States
PT  - Preprint
DEP - 20230724
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - ERJ Open Res. 2024 Feb 19;10(1):. PMID: 38375425
PMC - PMC10402235
COIS- COMPETING INTERESTS LJD, AS, MN, XRS and BLY are full-time employees of 
      Genentech; AS, MN, XRS, and BLY and hold stock options in Roche. JMO reports 
      personal fees from Boehringer Ingelheim, Genentech, United Therapeutics, AmMax 
      Bio and Lupin Pharmaceuticals outside of the submitted work. DAS is the founder 
      and chief scientific officer of Eleven P15, a company focused on the early 
      detection and treatment of pulmonary fibrosis. RGJ reports honoraria from Chiesi, 
      Roche, PatientMPower, AstraZeneca, GSK, Boehringer Ingelheim, and consulting fees 
      from Bristol Myers Squibb, Daewoong, Veracyte, Resolution Therapeutics, RedX, 
      Pliant, Chiesi. LVW reports research funding from GlaxoSmithKline, Roche and 
      Orion Pharma, and consultancy for GlaxoSmithKline and Galapagos, outside of the 
      submitted work. The other authors declare no competing interests.
EDAT- 2023/08/07 06:42
MHDA- 2023/08/07 06:43
PMCR- 2023/08/04
CRDT- 2023/08/07 04:42
PHST- 2023/08/07 06:42 [pubmed]
PHST- 2023/08/07 06:43 [medline]
PHST- 2023/08/07 04:42 [entrez]
PHST- 2023/08/04 00:00 [pmc-release]
AID - 2023.07.20.23292940 [pii]
AID - 10.1101/2023.07.20.23292940 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2023 Jul 24:2023.07.20.23292940. doi: 
      10.1101/2023.07.20.23292940.