INTRODUCTION: The objective of this study was to identify genetic variants that are associated with adult leisure time exercise behavior using genome-wide association (GWA) in two independent samples. METHODS: Exercise behavior was measured in 1644 unrelated Dutch and 978 unrelated American adults of European ancestry with detailed questions about type, frequency, and duration of exercise. Individuals were classified into regular exercisers or nonexercisers using a threshold of 4 MET·h (metabolic equivalents-hours per week). GWA analyses of ∼1.6 million observed and imputed Single Nucleotide Polymorphism (SNP) were conducted in both samples independently using logistic regression in SNPTEST, including sex, age, and body mass index as covariates. A meta-analysis of the results was performed using the weighted inverse variance method in METAL. RESULTS: Thirty-seven novel SNPs in the PAPSS2 gene and in two intergenic regions on chromosomes 2q33.1 and 18p11.32 were associated with exercise participation (pooled P values <1.0 × 10(-5)). Previously reported associations (ACE, CASR, CYP19A1, DRD2, LEPR, and MC4R genes) or linkage findings (2p22.3, 4q28, 4q31.21 7p13, 9q31, 11p15, 13q22, 15q13, 18q12.2, 18q21.1, 19p13.3, and 20q12) were not replicated, although suggestive evidence was found for association to rs12405556 in the LEPR gene (pooled P value 9.7 × 10(-4); American sample, P value 9.8 × 10(-5)) and for association to rs8036270 in the GABRG3 gene (pooled P value 4.6 × 10(-5)) in the linkage region 15q12-13. CONCLUSIONS: The heritability of leisure time exercise behavior is likely to be accounted for by many genetic variants with small effect size. These can be detected by GWA as was shown here for the PAPSS2 gene, but larger samples with genome-wide genotypes and high-quality exercise data are needed for further progress.
INTRODUCTION: The objective of this study was to identify genetic variants that are associated with adult leisure time exercise behavior using genome-wide association (GWA) in two independent samples. METHODS: Exercise behavior was measured in 1644 unrelated Dutch and 978 unrelated American adults of European ancestry with detailed questions about type, frequency, and duration of exercise. Individuals were classified into regular exercisers or nonexercisers using a threshold of 4 MET·h (metabolic equivalents-hours per week). GWA analyses of ∼1.6 million observed and imputed Single Nucleotide Polymorphism (SNP) were conducted in both samples independently using logistic regression in SNPTEST, including sex, age, and body mass index as covariates. A meta-analysis of the results was performed using the weighted inverse variance method in METAL. RESULTS: Thirty-seven novel SNPs in the PAPSS2 gene and in two intergenic regions on chromosomes 2q33.1 and 18p11.32 were associated with exercise participation (pooled P values <1.0 × 10(-5)). Previously reported associations (ACE, CASR, CYP19A1, DRD2, LEPR, and MC4R genes) or linkage findings (2p22.3, 4q28, 4q31.21 7p13, 9q31, 11p15, 13q22, 15q13, 18q12.2, 18q21.1, 19p13.3, and 20q12) were not replicated, although suggestive evidence was found for association to rs12405556 in the LEPR gene (pooled P value 9.7 × 10(-4); American sample, P value 9.8 × 10(-5)) and for association to rs8036270 in the GABRG3 gene (pooled P value 4.6 × 10(-5)) in the linkage region 15q12-13. CONCLUSIONS: The heritability of leisure time exercise behavior is likely to be accounted for by many genetic variants with small effect size. These can be detected by GWA as was shown here for the PAPSS2 gene, but larger samples with genome-wide genotypes and high-quality exercise data are needed for further progress.
Authors: Richa Saxena; Paul I W de Bakker; Karyn Singer; Vamsi Mootha; Noel Burtt; Joel N Hirschhorn; Daniel Gaudet; Bo Isomaa; Mark J Daly; Leif Groop; Kristin G Ardlie; David Altshuler Journal: Am J Hum Genet Date: 2006-05-24 Impact factor: 11.025
Authors: Dorret I Boomsma; Eco J C de Geus; Jacqueline M Vink; Janine H Stubbe; Marijn A Distel; Jouke-Jan Hottenga; Danielle Posthuma; Toos C E M van Beijsterveldt; James J Hudziak; Meike Bartels; Gonneke Willemsen Journal: Twin Res Hum Genet Date: 2006-12 Impact factor: 1.587
Authors: James Trevaskis; Ken Walder; Victoria Foletta; Lyndal Kerr-Bayles; Janine McMillan; Adrian Cooper; Scott Lee; Kristy Bolton; Matthew Prior; Richard Fahey; Kate Whitecross; Gregory J Morton; Michael W Schwartz; Greg R Collier Journal: Endocrinology Date: 2005-05-26 Impact factor: 4.736
Authors: Guowen Cai; Shelley A Cole; Nancy Butte; Carlos Bacino; Vincent Diego; Karen Tan; Harald H Göring; Stephen O'Rahilly; I Sadaf Farooqi; Anthony G Comuzzie Journal: Obesity (Silver Spring) Date: 2006-09 Impact factor: 5.002
Authors: Janine H Stubbe; Dorret I Boomsma; Jacqueline M Vink; Belinda K Cornes; Nicholas G Martin; Axel Skytthe; Kirsten O Kyvik; Richard J Rose; Urho M Kujala; Jaakko Kaprio; Jennifer R Harris; Nancy L Pedersen; Janice Hunkin; Tim D Spector; Eco J C de Geus Journal: PLoS One Date: 2006-12-20 Impact factor: 3.240
Authors: J Timothy Lightfoot; Larry Leamy; Daniel Pomp; Michael J Turner; Anthony A Fodor; Amy Knab; Robert S Bowen; David Ferguson; Trudy Moore-Harrison; Alicia Hamilton Journal: J Appl Physiol (1985) Date: 2010-06-10