Genetic variants underpinning lung function decline in the Lifelines general population cohort study.

Area of Science:

• Genetics
• Pulmonology
• Aging Research

Background:

• Age-related lung function decline is influenced by genetic and environmental factors.
• Understanding genetic contributions is crucial for identifying susceptibility and interventions.
• The Lifelines cohort study provides a valuable resource for investigating these genetic factors.

Purpose of the Study:

• To identify genetic variants associated with the rate of lung function decline.
• To explore the genetic underpinnings of individual differences in lung aging.
• To leverage large-scale cohort data for genetic discovery in lung function changes.

Main Methods:

• Utilized longitudinal spirometry data from 24,749 subjects over ~15 years.
• Employed linear mixed-effects models to estimate lung function change.
• Conducted a genome-wide association study (GWAS) and meta-analysis of selected single-nucleotide polymorphisms (SNPs).

Main Results:

• Identified 67 variants suggestively associated with lung function decline (p<1×10⁻⁵).
• A novel intergenic variant, rs150094594, reached genome-wide significance (p=3.9×10⁻⁹) for lung function decline.
• This variant demonstrated a consistent effect direction in replication cohorts.

Conclusions:

• Genetics plays a significant role in age-related lung function decline.
• Highlights the importance of investigating gene-environment interactions in lung aging.
• The identified variant rs150094594 offers a new target for understanding lung function trajectories.