Vasile Foris, MD, PhD, MSc
(He/Him/His)
Rank
Fellow or Postdoc
Department
Medicine
Channing Division of Network Medicine
Authors
Vasile Foris, MD, PhD, MSc*, Adel Boueiz MD, Kangjin Kim, PhD, Leonardo Martini, PhD, Courtney Tern, Raul San Jose Estepar, PhD, George Washko, MD, Edwin K. Silverman, MD, PhD, Michael H. Cho, MD for the COPDGene and TOPMed investigators.
Principal Investigator
Michael H. Cho
Twitter / Website
Categories
Introduction: Understanding the genetic background of chronic obstructive pulmonary disease (COPD) associated pulmonary hypertension could enhance disease classification. We aimed to evaluate known pathogenic variants of genes associated with pulmonary arterial hypertension (PAH) in a large cohort of smokers.
Methods: We analyzed whole genome sequencing and Phase 1 clinical data from the Genetic Epidemiology of COPD (COPDGene) cohort. We used WGSA v0.95 and ClinVar to annotate 26 genes with putative evidence for association with PAH.
Results: We analyzed 10,550 whole genomes and 133,060 intronic and exonic variants in previously identified PAH genes. Only 2,256 variants (1.7%) were reported in ClinVar, with 1,501 classified as benign/likely benign, 724 as variants of uncertain significance (VUS) or with conflicting interpretations, and 31 as pathogenic/likely pathogenic. Carriers of pathogenic variants (36 subjects, representing 0.3% of the COPDGene cohort), showed no differences in demographic factors, lung function, or pulmonary vascular imaging phenotypes compared to carriers of VUS (5,279 subjects) or benign variants (4,845 subjects) in both univariable or models adjusted for age, sex, race, and genetic ancestry.
Conclusion: Clinically annotated pathogenic variants in known PAH genes are rare in the COPDGene cohort. Future research will incorporate non-ClinVar variants and leverage longitudinal data for a more comprehensive understanding of these genetic influences.
