Sean Kalra, MD

(He/Him/His)

Rank

Fellow or Postdoc

Department

Medicine

Channing Division of Network Medicine

Authors

Sean Kalra*, MD, Qingwen Chen,MS, Courtney Tern MS, Chengyue Zhang, MS, Jessica Lasky-Su, PhD, Gary M. Hunninghake, MD,MPH, Edwin K. Silverman, MD,PhD, Richard Allen, PhD, Louise Wain, PhD, Matthew Moll, MD,MPH, Michael H. Cho1, MD,MPH

Principal Investigator

Michael Cho

Twitter / Website

Categories

The Association of a Polygenic Risk Score for Idiopathic Pulmonary Fibrosis with Transplant Free Survival in Biobank Cohorts

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Abstract

RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive lung scarring and high mortality. Genetic markers, aggregated into a polygenic risk score (PRS), are associated with IPF diagnosis in well-phenotyped case-control studies. However, the association of the PRS with transplant free survival is unknown.
METHODS: We conducted an observational study in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKBB). We evaluated the association of a binary high vs low risk PRS with the composite endpoint of lung transplant or mortality using multivariable cox proportional hazards models adjusting for age, gender, and principal components of ancestry.
RESULTS: Of 38,502 and 450,559 participants from MGBB and UKBB respectively, 1,034 (2.7%) and 2,760 (0.6%) participants had a diagnosis of IPF in the electronic healthcare record. Among those with IPF, a high risk PRS portends significantly increased hazards of mortality or transplant in MGBB (HR 1.58 95%CI 1.14-2.19) and UKBB (HR 1.23 95%CI 1.09-1.38).
CONCLUSIONS: The PRS association with the composite outcome of mortality or transplant demonstrates genetics can play a prognostic role in risk stratifying IPF with clinical ramifications.