Genetic Determinants for Leisure-Time Physical Activity.

Area of Science:

• Genetics
• Cardiovascular Health
• Exercise Science

Background:

• Leisure-time physical activity (LTPA) is crucial for cardiometabolic health.
• The genetic underpinnings of LTPA are not well understood.
• Limited research exists on the genetic architecture influencing physical activity levels.

Purpose of the Study:

• To comprehensively investigate the role of genetic factors in determining LTPA.
• To identify specific genetic variants associated with LTPA across diverse ethnic groups.
• To explore the genetic architecture influencing the capacity and motivation for physical activity.

Main Methods:

• Conducted a genomewide association study (GWAS) using imputed data from large cohorts (Women's Health Initiative, Jackson Heart Study, Framingham Heart Study).
• Performed ethnicity-specific analyses for African Americans and European Americans.
• Utilized secondary analyses including candidate gene, sequence kernel association tests, pathway, functional annotation, and expression quantitative trait loci (eQTL) analyses.

Main Results:

• Identified novel genetic variants associated with LTPA in African Americans (rs116550874, rs3792874) and European Americans (rs28524846).
• Replicated four previously reported LTPA-associated loci (GABRG3, CYP19A1, PAPSS2, CASR).
• Functional annotation suggests identified loci are involved in reward systems and the regulation of physical activity capacity.

Conclusions:

• This is the first comprehensive genomewide investigation of LTPA signals across multiple ethnicities.
• Findings provide strong evidence for a significant genetic predisposition in determining LTPA.
• Further research is warranted to explore the biological and clinical implications of these genetic findings.