Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies.

ABSTRACT:

Background

Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

Methods

We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups.

Findings

We examined

SUBMITTER: Moll M 

PROVIDER: S-EPMC11570824 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature