P191 Exploring the association between human leukocyte antigen (HLA) genetics and idiopathic pulmonary fibrosis
Year: 2023
Type: conference-abstract
Abstract: Introduction and Objective Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterised by progressive lung fibrosis. Recent studies support the role of infection in IPF development. The Human Leukocyte Antigen (HLA) region has a key role in immune response, and a previous study on idiopathic interstitial pneumonia (IIP) reported a statistically significant signal at HLA-DQB1. Here we aimed to explore the specific link between HLA genetic variation and IPF susceptibility. Methods We conducted a meta-analysis of association results from seven independent case-control studies of IPF, including the prior study of IIP. These comprised a total of 5,159 cases and 27,459 controls of European ancestry. We used an HLA-specific imputation approach to impute single nucleotide polymorphisms (SNPs), classical HLA alleles and amino acids, and performed logistic regression analyses individually for each study. After meta-analysis, we declared significance at p<4.5x10-4 after applying multiple test correction. We evaluated the consistency of association results across studies using MAMBA, designating variants with a posterior probability of replication >90% as robust. We also aimed to validate the previously reported association of HLA-DQB1 in the subset of IPF studies excluding the IIP study. Results The meta-analysis revealed four significant independent HLA variants associated with IPF risk. However, the effects were inconsistent across the contributing studies and therefore signals have a poor posterior probability for replication. The HLA-DQB1 association was not replicated in the independent IPF studies. Conclusions Variation in the HLA region was not consistently associated with IPF susceptibility in European ancestry populations, although it may have a role in other IIPs. Future studies are also needed to investigate if other immune system genes may be involved in the aetiology of IPF. Please refer to page A292 for declarations of interest related to this abstract.
Source: Thorax
Authors: B Guillen-Guio, ML Paynton, RJ Allen, DPW Chin, L Donoghue, A Stockwell, OC Leavy, T Hernandez-Beeftink, C Reynolds, P Cullinan, F Martinez, CleanUP-IPF Investigators of the Pulmonary Trials Cooperative, HL Booth, WA Fahy, IP Hall, SP Hart, MR Hill, N Hirani, RB Hubbard, RJ McAnulty, AB Millar, V Navaratnam, E Oballa, H Parfrey, G Saini, I Sayers, MD Tobin, MKB Whyte, A Adegunsoye, N Kaminski, SF Ma, ME Strek, Y Zhang, TE Fingerlin, M Molina-Molina, M Neighbors, XR Sheng, JM Oldham, TM Maher, DA Schwartz, PL Molyneaux, C Flores, I Noth, BL Yaspan, RG Jenkins, LV Wain, EJ Hollox
Institutions: University of Leicester, NIHR Leicester Biomedical Research Centre, Genentech, Imperial College London, Weill Cornell Medicine, University College Hospital, GlaxoSmithKline (United Kingdom), University of Nottingham, National Institute for Health and Care Research, Nottingham Biomedical Research Centre, University of Hull, University of Oxford, University of Edinburgh, University College London, University of Bristol, Nottingham University Hospitals NHS Trust, Prince Charles Hospital, Papworth Hospital NHS Foundation Trust, University of Chicago, Yale University, University of Virginia, University of Pittsburgh, National Jewish Health, Instituto de Salud Carlos III, Institut d'Investigació Biomédica de Bellvitge, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Universitat de Barcelona, University of Michigan, University of Southern California, University of Colorado Anschutz, Royal Brompton Hospital, Hospital Universitario Nuestra Señora de Candelaria, Universidad Fernando Pessoa Canarias, Instituto Tecnológico y de Energías Renovables
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4388424205