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Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time.

ABSTRACT: Genetic influence on lung functions has been identified in previous studies; however, the relative longitudinal effects of genetic factors and their interactions with smoking on lung function remain unclear. Here, we identified the longitudinal effects of genetic variants on lung function by determining single nucleotide polymorphism (SNP) heritability and genetic correlations, and by analyzing interactions with smoking. Subject-specific means and annual change rates were calculated for eight spirometric measures obtained from 6622 Korean adults aged 40-69 years every two years for 14 years, and their heritabilities were estimated separately. Statistically significant (p < 0.05) heritability for the subject-specific means of all spirometric measures (8~32%) and change rates of forced expiratory volume in 1 s to forced vital capacity ratio (FEV₁/FVC; 16%) and post-bronchodilator FEV₁/FVC (17%) were detected. Significant genetic correlations of the change rate with the subject-specific mean were observed for FEV₁/FVC (ρg = 0.64) and post-bronchodilator FEV₁/FVC (ρg = 0.47). Furthermore, post-bronchodilator FEV₁/FVC showed significant heritability of SNP-by-smoking interaction (hGXS2 = 0.4) for the annual change rate. The GWAS also detected genome-wide significant SNPs for FEV₁ (rs4793538), FEV₁/FVC (rs2704589, rs62201158, and rs9391733), and post-bronchodilator FEV₁/FVC (rs2445936). We found statistically significant evidence of heritability role on the change in lung function, and this was shared with the effects on cross-sectional measurements. We also found some evidence of interaction with smoking for the change of lung function.

SUBMITTER: Li D

PROVIDER: S-EPMC9316642 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction:Organizational readiness to change may be a key determinant of implementation success and a mediator of the effectiveness of implementation interventions. If organizational readiness can be reliably and validly assessed at the outset of a change initiative, it could be used to assess the effectiveness of implementation-support activities by measuring changes in readiness factors over time. Methods:We analyzed two waves of readiness-to-change survey data collected as part of a three-arm, randomized controlled trial to implement evidence-based health promotion practices in small worksites in low-wage industries. We measured five readiness factors: context (favorable broader conditions); change valence (valuing health promotion); information assessment (demands and resources to implement health promotion); change commitment (an intention to implement health promotion); and change efficacy (a belief in shared ability to implement health promotion). We expected commitment and efficacy to increase at intervention sites along with their self-reported effort to implement health promotion practices, termed wellness-program effort. We compared means between baseline and 15?months, and between intervention and control sites. We used linear regression to test whether intervention and control sites differed in their change-readiness scores over time. Results:Only context and change commitment met reliability thresholds. Change commitment declined significantly for both control (-0.39) and interventions sites (-0.29) from baseline to 15?months, while context did not change for either. Only wellness program effort at 15?months, but not at baseline, differed significantly between control and intervention sites (1.20 controls, 2.02 intervention). Regression analyses resulted in two significant differences between intervention and control sites in changes from baseline to 15?months: (1) intervention sites exhibited significantly smaller change in context scores relative to control sites over time and (2) intervention sites exhibited significantly higher changes in wellness program effort relative to control sites. Discussion:Contrary to our hypothesis, change commitment declined significantly at both Healthlinks and control sites, even as wellness-program effort increased significantly at HealthLinks sites. Regression to the mean may explain the decline in change commitment. Future research needs to assess whether baseline commitment is an independent predictor of wellness-program effort or an effect modifier of the HealthLinks intervention.

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Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time.

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