Genome-wide association study of exercise behavior in dutch and american adults

Marleen H M De Moor, Yong Jun Liu, Dorret I. Boomsma, Jian Li, James J. Hamilton, Jouke Jan Hottenga, Shawn Levy, Xiao Gang Liu, Yu Fang Pei, Danielle Posthuma, Robert R. Recker, Patrick F. Sullivan, Liang Wang, Gonneke Willemsen, Han Yan, Eco J C De Geus, Hong Wen Deng

Research output: Contribution to journalArticle

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Abstract

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 -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.

Original languageEnglish
Pages (from-to)1887-1895
Number of pages9
JournalMedicine and Science in Sports and Exercise
Volume41
Issue number10
DOIs
StatePublished - Oct 2009

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Genome-Wide Association Study
Exercise
Genes
Leisure Activities
Genome
Single Nucleotide Polymorphism
Metabolic Equivalent
Intergenic DNA
Meta-Analysis
Body Mass Index
Chromosomes
Logistic Models
Genotype

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

De Moor, M. H. M., Liu, Y. J., Boomsma, D. I., Li, J., Hamilton, J. J., Hottenga, J. J., ... Deng, H. W. (2009). Genome-wide association study of exercise behavior in dutch and american adults. Medicine and Science in Sports and Exercise, 41(10), 1887-1895. https://doi.org/10.1249/MSS.0b013e3181a2f646

Genome-wide association study of exercise behavior in dutch and american adults. / De Moor, Marleen H M; Liu, Yong Jun; Boomsma, Dorret I.; Li, Jian; Hamilton, James J.; Hottenga, Jouke Jan; Levy, Shawn; Liu, Xiao Gang; Pei, Yu Fang; Posthuma, Danielle; Recker, Robert R.; Sullivan, Patrick F.; Wang, Liang; Willemsen, Gonneke; Yan, Han; De Geus, Eco J C; Deng, Hong Wen.

In: Medicine and Science in Sports and Exercise, Vol. 41, No. 10, 10.2009, p. 1887-1895.

Research output: Contribution to journalArticle

De Moor, MHM, Liu, YJ, Boomsma, DI, Li, J, Hamilton, JJ, Hottenga, JJ, Levy, S, Liu, XG, Pei, YF, Posthuma, D, Recker, RR, Sullivan, PF, Wang, L, Willemsen, G, Yan, H, De Geus, EJC & Deng, HW 2009, 'Genome-wide association study of exercise behavior in dutch and american adults', Medicine and Science in Sports and Exercise, vol. 41, no. 10, pp. 1887-1895. https://doi.org/10.1249/MSS.0b013e3181a2f646
De Moor, Marleen H M ; Liu, Yong Jun ; Boomsma, Dorret I. ; Li, Jian ; Hamilton, James J. ; Hottenga, Jouke Jan ; Levy, Shawn ; Liu, Xiao Gang ; Pei, Yu Fang ; Posthuma, Danielle ; Recker, Robert R. ; Sullivan, Patrick F. ; Wang, Liang ; Willemsen, Gonneke ; Yan, Han ; De Geus, Eco J C ; Deng, Hong Wen. / Genome-wide association study of exercise behavior in dutch and american adults. In: Medicine and Science in Sports and Exercise. 2009 ; Vol. 41, No. 10. pp. 1887-1895.
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abstract = "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 -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.",
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AU - De Moor, Marleen H M

AU - Liu, Yong Jun

AU - Boomsma, Dorret I.

AU - Li, Jian

AU - Hamilton, James J.

AU - Hottenga, Jouke Jan

AU - Levy, Shawn

AU - Liu, Xiao Gang

AU - Pei, Yu Fang

AU - Posthuma, Danielle

AU - Recker, Robert R.

AU - Sullivan, Patrick F.

AU - Wang, Liang

AU - Willemsen, Gonneke

AU - Yan, Han

AU - De Geus, Eco J C

AU - Deng, Hong Wen

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N2 - 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 -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.

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