Genetic and Epigenetic Association of Lung Function and Chronic Obstructive Pulmonary Disease-Related Phenotypes in...

Chronic obstructive pulmonary disease (COPD) is influenced by environmental exposure and genetic susceptibility. Although large-scale genetic studies have identified loci associated with COPD and lung function, most evidence has come from populations of European ancestry, and data from Asian populations remain limited.

This scoping review aimed to summarize KoGES-based studies on genetic and epigenetic associations with COPD and COPD-related lung function phenotypes.

PubMed, Scopus, Web of Science, KoreaMed, RISS, KISS, and DBpia were searched from inception to April 27, 2026. Original studies using KoGES data to investigate genetic or epigenetic associations with COPD, airflow limitation, lung function traits, or longitudinal lung function decline were included. The review followed the Arksey and O'Malley framework and PRISMA-ScR guidance.

Of 20 unique records identified for final assessment, one conference abstract/preliminary report corresponding to a subsequently published full-length article was removed before screening. The remaining 19 records were screened, and 12 studies met the eligibility criteria. Most KoGES-based studies focused on spirometric traits, including FEV1, FEV1/FVC, and longitudinal lung function decline, rather than clinically defined COPD. Major approaches included genome-wide association studies (GWAS), exome array analysis, gene-environment interaction, polygenic/genetic risk score (PRS/GRS) analysis, epigenome-wide association studies (EWAS), and heritability analysis. Recurrent signals involved FAM13A and the 6p21/AGER region. Recent studies increasingly addressed longitudinal phenotypes, including rapid FEV1 decline and annual lung function decline.

KoGES-based studies provide population-specific evidence on genetic and epigenetic associations with COPD-related lung function phenotypes in Koreans. However, evidence for clinically defined COPD, externally validated risk prediction, and integrative multi-omics remains limited. Future studies should distinguish spirometric traits, longitudinal decline, and clinically defined COPD while validating KoGES findings in larger Asian and multi-ethnic populations.