A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities.

Autor:	Moll M; Division of Pulmonary and Critical Care Medicine, and.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Peljto AL; Department of Medicine and.; Department of Immunology, Division of Pulmonary Medicine, University of Colorado, Aurora, Colorado., Kim JS; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia., Xu H; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts., Debban CL; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia., Chen X; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Phoenix, Arizona., Menon A; Division of Pulmonary and Critical Care Medicine, and., Putman RK; Division of Pulmonary and Critical Care Medicine, and., Ghosh AJ; Department of Medicine, Division of Pulmonary and Critical Care Medicine, State University of New York Upstate Medical Center, Syracuse, New York., Saferali A; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Nishino M; Center for Pulmonary Functional Imaging, Department of Radiology., Hatabu H; Center for Pulmonary Functional Imaging, Department of Radiology., Hobbs BD; Division of Pulmonary and Critical Care Medicine, and.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Hecker J; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., McDermott G; Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Sparks JA; Division of Rheumatology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Wain LV; Department of Health Sciences, University of Leicester, Leicester, United Kingdom.; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom., Allen RJ; Department of Health Sciences, University of Leicester, Leicester, United Kingdom.; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom., Tobin MD; Department of Health Sciences, University of Leicester, Leicester, United Kingdom.; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom., Raby BA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.; Department of Pediatrics.; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts., Chun S; Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts., Silverman EK; Division of Pulmonary and Critical Care Medicine, and.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Zamora AC; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Phoenix, Arizona., Ortega VE; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Phoenix, Arizona., Garcia CK; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, New York., Barr RG; Department of Medicine and.; Division of General Medicine, Department of Epidemiology, Columbia University Medical Center, New York, New York., Bleecker ER; Division of Genetics, Genomics, and Precision Medicine, Department of Medicine, University of Arizona, Tucson, Arizona., Meyers DA; Division of Genetics, Genomics, and Precision Medicine, Department of Medicine, University of Arizona, Tucson, Arizona., Kaner RJ; Division of Pulmonary Medicine, Weill Cornell School of Medicine, New York, New York., Rich SS; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia., Manichaikul A; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, Virginia., Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles Medical Center, Torrance, California., Dupuis J; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.; Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada., O'Connor GT; Department of Medicine, Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts; and., Fingerlin TE; The National Jewish Health Cohen Family Asthma Institute, Division of Allergy and Immunology, National Jewish Health, Denver, Colorado., Hunninghake GM; Division of Pulmonary and Critical Care Medicine, and., Schwartz DA; Department of Medicine and.; Department of Immunology, Division of Pulmonary Medicine, University of Colorado, Aurora, Colorado., Cho MH; Division of Pulmonary and Critical Care Medicine, and.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2023 Oct 01; Vol. 208 (7), pp. 791-801.
DOI:	10.1164/rccm.202212-2257OC
Abstrakt:	Rationale: In addition to rare genetic variants and the MUC5B locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the MUC5B locus for IPF and interstitial lung abnormalities (ILAs) is unknown. Objectives: We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the MUC5B region on IPF, ILA, and ILA progression. Methods: We developed PRSs that included (PRS-M5B) and excluded (PRS-NO-M5B) the MUC5B region (500-kb window around rs35705950-T) using an IPF genome-wide association study. We assessed PRS associations with area under the receiver operating characteristic curve (AUC) metrics for IPF, ILA, and ILA progression. Measurements and Main Results: We included 14,650 participants (1,970 IPF; 1,068 ILA) from six multi-ancestry population-based and case-control cohorts. In cases excluded from genome-wide association study, the PRS-M5B (odds ratio [OR] per SD of the score, 3.1; P  = 7.1 × 10 -95 ) and PRS-NO-M5B (OR per SD, 2.8; P  = 2.5 × 10 -87 ) were associated with IPF. Participants in the top PRS-NO-M5B quintile had ∼sevenfold odds for IPF compared with those in the first quintile. A clinical model predicted IPF (AUC, 0.61); rs35705950-T and PRS-NO-M5B demonstrated higher AUCs (0.73 and 0.7, respectively), and adding both genetic predictors to a clinical model yielded the highest performance (AUC, 0.81). The PRS-NO-M5B was associated with ILA (OR, 1.25) and ILA progression (OR, 1.16) in European ancestry participants. Conclusions: A common genetic variant risk score complements the MUC5B variant to identify individuals at high risk of interstitial lung abnormalities and pulmonary fibrosis.
Databáze:	MEDLINE
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