Genome-wide SNP-sex interaction analysis of susceptibility to idiopathic pulmonary fibrosis.
| العنوان: | Genome-wide SNP-sex interaction analysis of susceptibility to idiopathic pulmonary fibrosis. |
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| المؤلفون: | Leavy OC; Department of Population Health Sciences, University of Leicester, Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Goemans AF; Department of Population Health Sciences, University of Leicester, Leicester, UK., Stockwell AD; Genentech, California, USA., Allen RJ; Department of Population Health Sciences, University of Leicester, Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Guillen-Guio B; Department of Population Health Sciences, University of Leicester, Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Hernandez-Beeftink T; Department of Population Health Sciences, University of Leicester, Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Adegunsoye A; University of Chicago, Chicago, USA., Booth HL; University College London Hospitals, London, UK., Cullinan P; Imperial College, London, UK., Fahy WA; GlaxoSmithKline, London, UK., Fingerlin TE; National Jewish Health, Colorado, USA., Virk HS; NIHR Leicester Biomedical Research Centre, Leicester, UK., Hall IP; University of Nottingham, Nottingham, UK.; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham, UK., Hart SP; University of Hull, Hull, UK., Hill MR; University of Oxford, Oxford, UK., Hirani N; University of Edinburgh, Edinburgh, UK., Hubbard RB; University of Nottingham, Nottingham, UK.; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham, UK., Kaminski N; Yale School of Medicine, Connecticut, USA., Ma SF; University of Virginia, Virginia, USA., McAnulty RJ; University College London, London, UK., Sheng XR; Genentech, California, USA., Millar AB; University of Bristol, Bristol, UK., Molina-Molina M; Servei de Pneumologia, Laboratori de Pneumologia Experimental, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain.; Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain., Navaratnam V; Department of Respiratory Medicine, Sir Charles Gardiner Hospital, Perth, Australia.; Centre for Respiratory Research, University of Western Australia, Perth, Australia., Neighbors M; Genentech, California, USA., Parfrey H; Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK., Saini G; University of Nottingham, Nottingham, UK., Sayers I; Centre for Respiratory Research, NIHR Nottingham Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK., Strek ME; University of Chicago, Chicago, USA., Tobin MD; Department of Population Health Sciences, University of Leicester, Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Whyte MK; University of Edinburgh, Edinburgh, UK., Zhang Y; University of Pittsburgh, Pittsburgh, USA., Maher TM; NIHR Imperial Biomedical Research Unit, National Heart and Lung Institute, Imperial College London, London, UK.; Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, USA., Molyneaux PL; National Institute for Health Research Respiratory Clinical Research Facility, Royal Brompton Hospital, London, UK.; NIHR Imperial Biomedical Research Unit, National Heart and Lung Institute, Imperial College London, London, UK., Oldham JM; University of Michigan, Michigan, USA., Yaspan BL; Genentech, California, USA., Flores C; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.; Genomics Division, Instituto Tecnologico y de Energias Renovables, Santa Cruz de Tenerife, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.; Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain., Martinez F; Weill Cornell Medicine, New York, USA., Reynolds CJ; Imperial College, London, UK., Schwartz DA; University of Colorado Medicine, Colorado, USA., Noth I; University of Virginia, Virginia, USA., Jenkins RG; NIHR Imperial Biomedical Research Unit, National Heart and Lung Institute, Imperial College London, London, UK., Wain LV; Department of Population Health Sciences, University of Leicester, Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK. |
| مؤلفون مشاركون: | CleanUP-IPF Investigators of the Pulmonary Trials Cooperative |
| المصدر: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 Jan 15. Date of Electronic Publication: 2024 Jan 15. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that is more prevalent in males than females. The reasons for this are not fully understood, with differing environmental exposures due to historically sex-biased occupations, or diagnostic bias, being possible explanations. To date, over 20 independent genetic variants have been identified to be associated with IPF susceptibility, but these have been discovered when combining males and females. Our aim was to test for the presence of sex-specific associations with IPF susceptibility and assess whether there is a need to consider sex-specific effects when evaluating genetic risk in clinical prediction models for IPF. Methods: We performed genome-wide single nucleotide polymorphism (SNP)-by-sex interaction studies of IPF risk in six independent IPF case-control studies and combined them using inverse-variance weighted fixed effect meta-analysis. In total, 4,561 cases (1,280 females and 2,281 males) and 23,500 controls (8,360 females and 14,528 males) of European genetic ancestry were analysed. We used polygenic risk scores (PRS) to assess differences in genetic risk prediction between males and females. Findings: Three independent genetic association signals were identified. All showed a consistent direction of effect across all individual IPF studies and an opposite direction of effect in IPF susceptibility between females and males. None had been previously identified in IPF susceptibility genome-wide association studies (GWAS). The predictive accuracy of the PRSs were similar between males and females, regardless of whether using combined or sex-specific GWAS results. Interpretation: We prioritised three genetic variants whose effect on IPF risk may be modified by sex, however these require further study. We found no evidence that the predictive accuracy of common SNP-based PRSs varies significantly between males and females. Competing Interests: AA declares funding from NIH (K23HL146942); consulting fees from Genentech, Inogen, Medscape, Abbvie, PatientMpower and Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim. ADS is a full-time employee of Genentech/Roche with stock and stock options in Roche. AFG was a full-time employee of PPD, Part of Thermo Fisher Scientific until June 2023. BGG declares fellowship funding from Wellcome Trust (221680/Z/20/Z). BLY is a full-time employee of Genentech/Roche with stock and stock options in Roche. CF declares funding Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III and Instituto Tecnológico y de Energías Renovables; honoraria in educational events from Fundación Instituto Roche. DAS declares being the founder and chief scientific officer of Eleven P15, Inc., a company dedicated to the early diagnosis and treatment of pulmonary fibrosis. HP declares grant payment to institution from Boehringer Ingelheim Ltd; consulting fees from Boehringer Ingelheim Ltd, Roche Limited, Trevi Therapeutics, Pilant Therapeutics; speaker fees from Boehringer Ingelheim Ltd; member of TIPAL trial management group, trustee for Action for Pulmonary Fibrosis, member of scientific advisory board for European Pulmonary Fibrosis Federation. IN declares funding from National Institutes of Health (UG3HL145266) to institution; grant funding to institution from Veracyte; consulting fees from Boerhinger Ingelheim and Sanofi. IPH declares funding from Wellcome Trust and NIHR; vice chair Trustees for Asthma + Lung UK. JMO declares funding from National Institutes of Health (R01HL169166 & K23HL138190); consulting fees from Boehringer Ingelheim, Lupin pharmaceuticals, AmMax Bio, Roche and Veracyte; patent for TOLLIP TT genotype for NAC use in IPF; participation on a Data Safety Monitoring Board or Advisory Board for Endeavor Biomedicines, Novartis and Genentech; Associate editor for CHEST, on Program Committee for American Thoracic Society and Editorial board for AJRCCM. LVW declares funding from UK Research and Innovation (MR/V00235X/1) and GSK/Asthma + Lung UK (Professorship (C17-1)) to complete this work; funding from Orion Pharma, GSK, Genentech, AstraZeneca, Nordic Bioscience, Sysmex (OGT); Consulting fees Galapagos, Boehringer Ingelheim, GSK; support for attending meetings and/or travel Genentech; participation on Advisory Board for Galapagos; leadership or fiduciary roles as Associate Editor for European Respiratory Journal and Medical Research Council Board member and Deputy Chair. MKBW declares funding from National Institutes of Health (K23HL146942); consulting fees from Genentech, Inogen, Medscape, Abbvie, PatientMpower and Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim. MN is a full-time employee of Genentech/Roche with stock and stock options in Roche. NK declares grant funding from National Institutes of Health; grant funding to institution from BMS, Boehringer Ingelheim and Three Lakes Foundation; consultancy fees from Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Theravance, Three Lake Partners, Astra Zeneca, RohBar, Veracyte, Augmanity, CSL Behring, Thyron, Gilead, Galapagos, Chiesi, Arrowhead, Sofinnova, GSK and Merk; patent for new therapies for IPF (Biotech), new therapies for ARDS (Biotech) and new Biomarkers in IPF (Biotech); equity in Pilant and Thyron; reports serving as the scientific founder of Thyron. PLM declares grant funding to institution from AstraZeneca; consultancy fees from Hoffman-La Roche, Boehringer Ingelheim, AstraZeneca, Trevi and Qureight; speaker fees from Boehringer Ingelheim and Hoffman-La Roche. RGJ declares funding from UK Research and Innovation (MR/V00235X/1); that their institute received funding from Astra Zeneca, Biogen, Galecto, GlaxoSmithKline, Nordic Biosciences, RedX and Pliant; consulting fees from AstraZeneca, Brainomix, Bristol Myers Squibb, Chiesi, Cohbar, Daewoong, GlaxoSmithKline, Veracyte, Resolution Therapeutics and Pliant; payment for lectures and presentations received from Boehringer Ingelheim, Chiesi, Roche, PatientMPower, AstraZeneca; payment for expert testimony from Pinsent Masons LLP; participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim, Galapagos, Vicore; leadership or fiduciary role for NuMedii and president for Action for Pulmonary Fibrosis. SPH declares grant funding to institution from Boehringer Ingelheim; consulting fees from Trevi therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi and Trevi therapeutics; support for attending meetings and/or travel from Chiesi; Participation on a Data Safety Monitoring Board or Advisory Board for Trevi therapeutics; Chair for BTS Standards of Care Committee (till November 2022) and Trustee for Action for Pulmonary Fibrosis. TMM declares consulting fees from Boehringer Ingelheim, Roche/Genentech, Astra Zeneca, Bayer, Blade Therapeutics, Bristol-Myers Squibb, CSL Behring, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pfizer, Pliant, Respivant, Sanofi, Theravance, Trevi, Veracyte and Vicore; participation on a Data Safety Monitoring Board or Advisory Board for Fibrogen, Blade Therapeutics and Nerre. XRS is a full-time employee of Genentech/Roche with stock and stock options in Roche. |
| معلومات مُعتمدة: | R01 HL141852 United States HL NHLBI NIH HHS; K23 HL146942 United States HL NHLBI NIH HHS; R01 HL127349 United States HL NHLBI NIH HHS; R01 HL166290 United States HL NHLBI NIH HHS; R01 HL169166 United States HL NHLBI NIH HHS; K23 HL138190 United States HL NHLBI NIH HHS; U01 HL145567 United States HL NHLBI NIH HHS; UG3 HL145266 United States HL NHLBI NIH HHS; United Kingdom WT_ Wellcome Trust; R21 HL161723 United States HL NHLBI NIH HHS |
| تواريخ الأحداث: | Date Created: 20240131 Latest Revision: 20240319 |
| رمز التحديث: | 20240319 |
| مُعرف محوري في PubMed: | PMC10827242 |
| DOI: | 10.1101/2024.01.12.24301204 |
| PMID: | 38293162 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.01.12.24301204 |
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