Genomewide Association Study of Leisure-Time Exercise Behavior in Japanese Adults

Area of Science:

• Genetics
• Exercise Physiology
• Behavioral Science

Background:

• Genetic factors are suspected to influence leisure-time exercise behavior.
• Previous genomewide association studies (GWAS) and candidate gene studies have yielded inconsistent results.
• A significant genomewide association for exercise behavior has not been established.

Purpose of the Study:

• To conduct a two-stage GWAS and candidate SNP association study to identify genetic variants associated with leisure-time exercise behavior.
• To validate findings from discovery samples in an independent replication cohort.
• To investigate potential links between identified genetic variants and gene expression in relevant tissues.

Main Methods:

• A two-stage GWAS and candidate single-nucleotide polymorphism (SNP) association study was performed on 13,980 discovery samples (J-MICC study) and 2036 replication samples (Aichi Cancer Center).
• Leisure-time physical activity was assessed via self-administered questionnaires, defining exercise behavior as ≥4 MET·h·wk.
• Association testing utilized mixed linear regression models, followed by meta-analysis of combined results. Six candidate SNPs were also tested.

Main Results:

• A novel SNP, rs10252228, located between NPSR1 and DPY19L1, showed significant association with leisure-time exercise behavior in both discovery and replication samples (combined P = 2.2 × 10⁻¹¹).
• SNPs linked to rs10252228 were associated with the gene expression of DPY19L1 and DP19L2P1 in multiple tissues, including skeletal muscle and heart.
• One candidate SNP, rs12612420 in DNAPTP6, showed nominal significance in discovery but not replication samples.

Conclusions:

• A novel genetic variant (rs10252228) significantly associated with regular leisure-time exercise behavior has been identified.
• The identified variant may influence exercise behavior through its association with DPY19L1 and DP19L2P1 gene expression.
• Further functional studies are necessary to elucidate the precise role of these genetic variants in exercise behavior.