Genetics of interstitial lung diseases: a state-of-the-art review

Nicole Ng¹, Maria Molina-Molina², Ayodeji Adegunsoye³, Raphael Borie⁴, Chad A Newton⁵, Benjamin Raby⁶, David Zhang⁷, Maria Padilla¹, Bruno Crestani⁴, Marshall S Horwitz⁸, Siobán Keel⁹, Michael F Murray¹⁰, Andrew B Stergachis^{11

12}, Shandra Knight¹³, Christine K Garcia⁷, Louise V Wain^{14

15}, Ganesh Raghu¹⁶

Affiliations

¹ Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² ILD Unit, Respiratory Department, University Hospital of Bellvitge, Biomedical Research Institute of Bellvitge (IDIBELL), University of Barcelona, CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain.
³ Section of Pulmonary and Critical Care, Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine, The University of Chicago, Chicago, IL, USA.
⁴ Université Paris Cité, UMR Inserm 1149, CRI, Hôpital Bichat, AP-HP, Service de Pneumologie Allergologie et Transplantation, Centre Constitutif du Centre de Référence des Maladies Pulmonaires Rares, FHU INFIRE, Paris, France.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁶ Division of Pulmonary Medicine, Boston Children's Hospital, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
⁸ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁹ Division of Hematology and Oncology, University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁰ Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
¹² Department of Genome Sciences, University of Washington, Seattle, WA, USA.
¹³ Strauss Health Sciences Library, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹⁴ Department of Population Health Sciences, University of Leicester, Leicester, UK.
¹⁵ Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester, Leicester, UK.
¹⁶ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA graghu@uw.edu.

PMID: 40841141
DOI: 10.1183/13993003.00788-2025

Review

Genetics of interstitial lung diseases: a state-of-the-art review

Nicole Ng et al. Eur Respir J. 2025.

. 2025 Sep 25;66(3):2500788.

doi: 10.1183/13993003.00788-2025. Print 2025 Sep.

Authors

Affiliations

¹ Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² ILD Unit, Respiratory Department, University Hospital of Bellvitge, Biomedical Research Institute of Bellvitge (IDIBELL), University of Barcelona, CIBER of Respiratory Diseases (CIBERES), Barcelona, Spain.
³ Section of Pulmonary and Critical Care, Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine, The University of Chicago, Chicago, IL, USA.
⁴ Université Paris Cité, UMR Inserm 1149, CRI, Hôpital Bichat, AP-HP, Service de Pneumologie Allergologie et Transplantation, Centre Constitutif du Centre de Référence des Maladies Pulmonaires Rares, FHU INFIRE, Paris, France.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁶ Division of Pulmonary Medicine, Boston Children's Hospital, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
⁸ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁹ Division of Hematology and Oncology, University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁰ Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
¹² Department of Genome Sciences, University of Washington, Seattle, WA, USA.
¹³ Strauss Health Sciences Library, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹⁴ Department of Population Health Sciences, University of Leicester, Leicester, UK.
¹⁵ Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester, Leicester, UK.
¹⁶ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA graghu@uw.edu.

PMID: 40841141
DOI: 10.1183/13993003.00788-2025

Abstract

Advancements in genetics and genomics continue to further our understanding of their contributions to the development of interstitial lung diseases (ILDs). This state-of-the-art clinical review synthesises current knowledge of the contribution of genetics when evaluating patients suspected to have ILD. We consider highly penetrant Mendelian disorders as well as common variants conferring smaller risk that act in concert with other genetic and acquired risk factors. Additionally, gene-by-environment and pharmacogenomic interactions are discussed to highlight their impact on disease course. Lastly, the approach to genetic ILDs is reviewed from available testing to future directions.

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Conflict of interest statement

Conflict of interest: N. Ng reports consultancy fees and support for attending meetings from Sanofi, and receipt of equipment, materials, drugs, medical writing, gifts or other services from Philips (Lumify). M. Molina-Molina reports grants from Roche and Boehringer Ingelheim, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Ferrer, and support for attending meetings from Boehringer Ingelheim. A. Adegunsoye reports grants from the NIH (K23HL146942), consultancy fees from Genentech, Inogen, Medscape, AbbVie, PatientMpower, Baxter, Brainomix, PureTech, GossamerBio and Boehringer Ingelheim, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim. R. Borie reports consultancy fees from Boehringer Ingelheim, Ferrer and Sanofi, and payment or honoraria for lectures, presentations, manuscript writing or educational events, and support for attending meetings from Boehringer Ingelheim. C.A. Newton grants from the NIH NHLBI, consultancy fees from Boehringer Ingelheim and Medpace Inc., and leadership roles with CHEST Journal (Editorial Board), Pulmonary Fibrosis Foundation (Strategic Planning Committee) and American Thoracic Society (Program Committee, Planning Committee, Executive Committee CP Assembly). D. Zhang reports support for the present study from the NIH NHLBI (K08HL169926), grants from the Francis Family Foundation (Parker B. Francis Fellowship Award), consultancy fees from Boehringer Ingelheim, and a leadership role with the American Thoracic Society (Executive Committee for Section on Genetics and Genomics). M. Padilla reports grants from Boehringer Ingelheim and Pfizer, and consultancy fees, support for attending meetings and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim and United Therapeutics. B. Crestani reports grants from Boehringer Ingelheim, consultancy fees from BMS, Boehringer Ingelheim, Chiesi, CSL Behring, GSK and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, BMS, Boehringer Ingelheim, GSK, Novartis, Roche and Sanofi, support for attending meetings from AstraZeneca, BMS, Boehringer Ingelheim, Roche and Sanofi, participation on a data safety monitoring board or advisory board with BMS, Boehringer Ingelheim, Horizon and Sanofi, and a leadership role with the Fondation du Souffle (President of the Board of Trustees). M.F. Murray reports an unpaid leadership role with the American College of Medical Genetics Board of Directors (6-year term ending March 2025). S. Knight reports consultancy fees from the PI for search services. C.K. Garcia reports support for the present study from the NIH (R01HL093096), grants from the DOD, NIH and foundation grants, a leadership role with the NIH ClinGen Pulmonary Domain (Co-Chair) and ILD GCEP (Co-Chair), stock (or stock options) with Rejuvenation Technologies, Inc. and the following financial (or non-financial) interests: AstraZeneca (research funding paid to institution outside the scope of this work). L.V. Wain reports grants from Orion Pharma, GSK, Genentech/Roche, Medical Research Council, Wellcome Trust, AstraZeneca, Nordic Bioscience and Sysmex (OGT), consultancy fees from Galapagos, Boehringer Ingelheim and GSK, support for attending meetings from Genentech, participation on a data safety monitoring board or advisory board with Galapagos, and leadership roles with the European Respiratory Journal (Associate Editor) and Medical Research Council (Board member and Deputy Chair). G. Raghu reports consultancy fees and support for attending meetings from Sanofi, and leadership roles with the Pulmonary Fibrosis Foundation (Scientific Advisory Board) and American Thoracic Society (Guideline Development). The remaining authors have no potential conflicts of interest to disclose.

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Genetics of interstitial lung diseases: a state-of-the-art review

Affiliations

Genetics of interstitial lung diseases: a state-of-the-art review

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources

Medical