Obesity-Related Genetic Variants and their Associations with Physical Activity.
BACKGROUND
Meta-analysis of genome-wide association studies identified obesity-related genetic variants. Due to the pleiotropic effects of related phenotypes, we tested six of these obesity-related genetic variants for their association with physical activity: fat mass and obesity-associated (FTO)(rs9939609)T>A, potassium channel tetramerization domain containing (KCTD15) (rs11084753)G>A, melanocortin receptor4 (MC4R)(rs17782313)T>C, neuronal growth regulator 1 (NEGR1)(rs2815752)A>G, SH2B adapter protein 1 (SH2B1)(rs7498665)A>G, and transmembrane protein18 (TMEM18)(rs6548238)C>T.


METHODS
European-American women (n= 263) and men (n= 229) (23.5 ± 0.3 years, 24.6 ± 0.2 kg/m2) were genotyped and completed the Paffenbarger physical activity Questionnaire. Physical activity volume in metabolic energy equivalents [MET]-hour/week was derived from the summed time spent (hour/week) times the given MET value for vigorous, moderate, and light intensity physical activity, and sitting and sleeping, respectively. Multivariable adjusted [(age, sex, and body mass index (BMI)] linear regression tested associations among genotype (dominant/recessive model) and the log of physical activity volume.


RESULTS
MC4R(rs17782313)T>C explained 1.1 % (p= 0.02),TMEM18(rs6548238)C>T 1.2 % (p= 0.01), andSH2B1(rs7498665)A>G 0.6 % (p= 0.08) of the variability in physical activity volume. Subjects with theMC4RC allele spent 3.5 % less MET-hour/week than those with the TT genotype (p= 0.02). Subjects with theTMEM18T allele spent 4.1 % less MET-hour/week than those with the CC genotype (p= 0.01). Finally, subjects with theSH2B1GG genotype spent 3.6 % less MET-hour/week than A allele carriers (p= 0.08).


CONCLUSIONS
Our findings suggest a shared genetic influence among some obesity-related gene loci and physical activity phenotypes that should be explored further. Physical activity volume differences by genotype have public health importance equating to 11-13 lb weight difference annually.
Department of Behavioral and Social Sciences, Brown University School of Public Health, Box G-S121-2, Providence, RI 02912 USA.
Harold
H
Lee
Department of Kinesiology, University of Connecticut, Storrs, CT 06269 USA.
Garrett I
GI
Ash
Obesity Center & School of Health Sciences, Emory & Henry College, Marion, VA 24354 USA.
Theodore J
TJ
Angelopoulos
Department of Health, Human Performance and Recreation, Baylor University, Waco, TX 76798 USA.
Paul M
PM
Gordon
Department of Sport Science and Health, Dublin City University, Dublin, 7008802 Ireland.
Niall M
NM
Moyna
Exercise & Sport Performance, University of New England, Biddeford, ME 04005 USA.
Paul S
PS
Visich
Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL 33431 USA.
Robert F
RF
Zoeller
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010 USA.
Heather
H
Gordish-Dressman
Department of Statistics, University of Connecticut, Storrs, CT 06269 USA.
Ved
V
Deshpande
Department of Statistics, University of Connecticut, Storrs, CT 06269 USA.
Ming-Hui
MH
Chen
Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, CT 06102 USA.
Paul D
PD
Thompson
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010 USA.
Eric P
EP
Hoffman
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010 USA.
Joseph M
JM
Devaney
Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269 USA ; Department of Kinesiology, University of Connecticut, Storrs, CT 06269 USA.
Linda S
LS
Pescatello