Polygenic scores for low lung function and the future risk of adverse health outcomes.

ABSTRACT

AIMS: Reduced lung function and adverse health outcomes are often observed. This study characterizes genetic susceptibility for reduced lung function and risk of developing a range of adverse health outcomes. METHODS: We studied 27,438 middle-aged adults from the Malmö Diet and Cancer study (MDCS), followed up to 28.8 years. Trait-specific Polygenic scores (PGS) for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were constructed for each participant using MDCS genetic data and summary statistics from the latest GWAS of lung function. Linear regression models and cox proportional hazards regression models were used to assess associations between adverse health outcomes and lung function-PGS. RESULTS: FEV1-PGS and FVC-PGS were significantly associated with mean sBP at baseline after adjustments (FEV1-PGS Q1 (highest PGS = highest lung function) 140.7mmHg vs. Q4 141.5mmHg, p-value 0.008). A low FVC-PGS was significantly associated with the risk of future diabetic events after adjustments (Q4 vs. Q1 HR 1.22 (CI 1.12-1.32), p-trend < 0.001) and had added value to risk prediction models for diabetes. Low FEV1-PGS was significantly associated with future coronary events (Q4 vs. Q1 HR 1.13 (CI 1.04-1.22), p-trend 0.008). No significant association was found between PGS and sudden cardiac death, chronic kidney disease or all-cause mortality. Results remained largely unchanged in a subgroup of subjects when further adjusted for apolipoproteins. CONCLUSION: Genetic susceptibility for reduced lung function is associated with higher sBP, increased risk of diabetes and to a lesser extent, future coronary events, suggesting etiological roles of lung function on these outcomes. Using PGS, high-risk groups could be early detected to implement early lifestyle changes to mitigate the risk.