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Publications

Journal Article Ahead of print

PubMed: 42085270 DOI: 10.1093/ajrccm/aamag152

Idiopathic Pulmonary Fibrosis Risk Loci in East Asian Populations Mirror those of European Populations.

Am J Respir Crit Care Med

Authors: Anna L Peljto, Haruhiko Furusawa, Deepa Puthenvedu, Joyce S Lee, Mark P Steele, Janna Brancato, Jonathan Cardwell, Rachel Z Blumhagen, Joao De Andrade, Elisabeth Bendstrup, Timothy S Blackwell, Francesco Bonella, Raphael Borie, Rebecca Braybrooke, Kevin K Brown, Roberto G Carbone, Jason D Christie, Ulrich Costabel, Bruno Crestani, Jesper R Davidsen, Philippe Dieude, Seamas C Donnelly, Jim Egan, Oliver Eickelberg, Evans R Fernández Pérez, Christine A Fiddler, Elena E Foster, Kevin F Gibson, Gunnar Gudmundsson, Joel M Guthridge, Michael T Henry, Nikhil Hirani, R Gisli Jenkins, Daniel J Kass, Michael P Keane, Nurdan Kokturk, Jonathan A Kropski, David Lederer, Paolo M Leone, Angela L Linderholm, Toby M Maher, Susan K Mathai, Cormac Mccarthy, Aoife N Mcelroy, Nesrin Mogulkoc, Maria Molina-Molina, Philip L Molyneaux, Sydney B Montesi, Steven D Nathan, Imre Noth … and 51 other authors

Affiliations

  • Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Tokyo Medical and Dental University, Tokyo, Japan.
  • Center for Genes, Environment, and Health, National Jewish Health, Denver, CO.
  • Vanderbilt University Medical Center, Nashville, TN.
  • Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark.
  • Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Center for Interstitial and Rare Lung Diseases, Ruhrlandklinik University Hospital, University of Duisburg-Essen, Essen, Germany.
  • Service de Pneumologie A, Hopital Bichat, Paris, France.
  • Respiratory Medicine, University of Nottingham, Nottingham, United Kingdom.
  • Department of Medicine, National Jewish Health, Denver, CO.
  • Department of Internal Medicine, University of Genoa, Genoa, Italy.
  • University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
  • Université Paris Cité, Inserm, Physiopathologie et Épidémiologie des Maladies Respiratoires, Paris, France.
  • South Danish Center for Interstitial Lung Diseases, Department of Respiratory Medicine, Odense University Hospital, Denmark.
  • Rheumatology Department, Bichat hospital, Paris, France.
  • Trinity College Dublin, Dublin, Ireland.
  • National Lung Transplantation Centre, Mater Misericordiae University Hospital, Dublin, Ireland.
  • Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
  • Royal Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom.
  • Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California-Davis, School of Medicine, Sacramento, CA.
  • University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
  • Oklahoma Medical Research Foundation, Oklahoma City, OK.
  • University of Oklahoma Health Sciences Center, Oklahoma City, OK.
  • Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland.
  • University of Edinburgh, Edinburgh, United Kingdom.
  • National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • School of Medicine, University College Dublin, Ireland.
  • St Vincent's University Hospital, Dublin, Ireland.
  • Faculty of Medicine, Department of Pulmonary Medicine, Gazi University, Ankara Türkiye.
  • Regeneron Pharmaceuticals, Inc, Tarrytown, NY.
  • San Raffaele IRCCS, Rome, Italy.
  • Università Cattolica del Sacro Cuore, Rome, Italy.
  • Department of Internal Medicine, University of California Davis, Davis, CA.
  • Keck Medicine of University of Southern California, Los Angeles, California.
  • Baylor University Medical Center, Dallas, TX.
  • Texas A&M University College of Medicine, Dallas, TX.
  • Department of Pulmonology, Ege University Hospital, Izmir, Turkey.
  • Respiratory Department, University Hospital of Bellvitge, University of Barcelona, Barcelona, Spain.
  • Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA.
  • Inova Fairfax Hospital, Falls Church, VA.
  • Department of Medicine, University of Virginia, Charlottesville, VA.

Abstract

RATIONALE

Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations.

OBJECTIVE

To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations.

METHODS

We included 1,026 patients with IPF and compared them to 1,723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject.

RESULTS

We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations.

CONCLUSIONS

We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

MeSH

Idiopathic Pulmonary Fibrosis, Promoter Regions, Genetic, Fibrosis, Genome-Wide Association Study, Critical Care, Pulmonary Fibrosis, Chromosomes