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Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry
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نویسنده
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ahmad s. ,rukh g. ,varga t.v. ,ali a. ,kurbasic a. ,shungin d. ,ericson u. ,koivula r.w. ,chu a.y. ,rose l.m. ,ganna a. ,qi q. ,stančáková a. ,sandholt c.h. ,elks c.e. ,curhan g. ,jensen m.k. ,tamimi r.m. ,allin k.h. ,jørgensen t. ,brage s. ,langenberg c. ,aadahl m. ,grarup n. ,linneberg a. ,paré g. ,magnusson p.k.e. ,pedersen n.l. ,boehnke m. ,hamsten a. ,mohlke k.l. ,pasquale l.t. ,pedersen o. ,scott r.a. ,ridker p.m. ,ingelsson e. ,laakso m. ,hansen t. ,qi l. ,wareham n.j. ,chasman d.i. ,hallmans g. ,hu f.b. ,renström f. ,orho-melander m. ,franks p.w.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 7
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چکیده
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Numerous obesity loci have been identified using genome-wide association studies. a uk study indicated that physical activity may attenuate the cumulative effect of 12 of these loci,but replication studies are lacking. therefore,we tested whether the aggregate effect of these loci is diminished in adults of european ancestry reporting high levels of physical activity. twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. a genetic risk score (grs) was calculated by summing the bmi-associated alleles of each genetic variant. physical activity was assessed using self-administered questionnaires. multiplicative interactions between the grs and physical activity on bmi were tested in linear and logistic regression models in each cohort,with adjustment for age,age2,sex,study center (for multicenter studies),and the marginal terms for physical activity and the grs. these results were combined using meta-analysis weighted by cohort sample size. the meta-analysis yielded a statistically significant grs × physical activity interaction effect estimate (pinteraction = 0.015). however,a statistically significant interaction effect was only apparent in north american cohorts (n = 39,810,pinteraction = 0.014 vs. n = 71,611,pinteraction = 0.275 for europeans). in secondary analyses,both the fto rs1121980 (pinteraction = 0.003) and the sec16b rs10913469 (pinteraction = 0.025) variants showed evidence of snp × physical activity interactions. this meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a grs in obesity disposition,although these findings hinge on the inclusion of cohorts from north america,indicating that these results are either population-specific or non-causal. © 2013 ahmad et al.
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آدرس
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genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, diabetes and cardiovascular disease - genetic epidemiology,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö,sweden,diabetes epidemiology research group,steno diabetes center,gentofte, Denmark, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö,sweden,department of public health and clinical medicine,section for medicine,umeå university,umeå,sweden,department of odontology,umeå university,umeå, Sweden, diabetes and cardiovascular disease - genetic epidemiology,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, division of preventive medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, division of preventive medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, department of nutrition,harvard school of public health,boston,ma, United States, department of medicine,university of eastern finland,kuopio, Finland, the novo nordisk foundation center for basic metabolic research,section of metabolic genetics,faculty of health and medical sciences,university of copenhagen,copenhagen, Denmark, mrc epidemiology unit,institute of metabolic science,addenbrooke's hospital,cambridge, United Kingdom, department of epidemiology,harvard school of public health,boston,ma,united states,channing division of network medicine,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, department of nutrition,harvard school of public health,boston,ma, United States, department of epidemiology,harvard school of public health,boston,ma,united states,channing division of network medicine,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, the novo nordisk foundation center for basic metabolic research,section of metabolic genetics,faculty of health and medical sciences,university of copenhagen,copenhagen, Denmark, research centre for prevention and health,glostrup university hospital,glostrup, Denmark, mrc epidemiology unit,institute of metabolic science,addenbrooke's hospital,cambridge, United Kingdom, mrc epidemiology unit,institute of metabolic science,addenbrooke's hospital,cambridge, United Kingdom, research centre for prevention and health,glostrup university hospital,glostrup, Denmark, the novo nordisk foundation center for basic metabolic research,section of metabolic genetics,faculty of health and medical sciences,university of copenhagen,copenhagen, Denmark, research centre for prevention and health,glostrup university hospital,glostrup, Denmark, department of pathology and molecular medicine,mcmaster university,hamilton,on,canada,genetic and molecular epidemiology laboratory,mcmaster university,hamilton,on,canada,population health research institute,hamilton,on, Canada, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, department of biostatistics and center for statistical genetics,university of michigan school of public health,ann arbor,mi, United States, cardiovascular genetics and genomics group,atherosclerosis research unit,department of medicine,solna,karolinska institutet,stockholm, Sweden, department of genetics,university of north carolina,chapel hill,nc, United States, department of ophthalmology,the mass eye and ear infirmary,harvard medical school,boston,ma, United States, the novo nordisk foundation center for basic metabolic research,section of metabolic genetics,faculty of health and medical sciences,university of copenhagen,copenhagen,denmark,faculty of health and medical sciences,university of copenhagen,copenhagen,denmark,faculty of health sciences,university of aarhus,aarhus, Denmark, mrc epidemiology unit,institute of metabolic science,addenbrooke's hospital,cambridge, United Kingdom, division of preventive medicine,brigham and women's hospital and harvard medical school,boston,ma,united states,division of cardiology,brigham and women's hospital and harvard medical school,boston,ma, United States, department of medical sciences,molecular epidemiology and science for life laboratory,uppsala university,uppsala, Sweden, department of medicine,university of eastern finland,kuopio,finland,kuopio university hospital,kuopio, Finland, the novo nordisk foundation center for basic metabolic research,section of metabolic genetics,faculty of health and medical sciences,university of copenhagen,copenhagen,denmark,faculty of health and medical sciences,university of copenhagen,copenhagen,denmark,faculty of health sciences,university of southern denmark,odense, Denmark, department of nutrition,harvard school of public health,boston,ma,united states,department of epidemiology,harvard school of public health,boston,ma,united states,channing division of network medicine,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, mrc epidemiology unit,institute of metabolic science,addenbrooke's hospital,cambridge, United Kingdom, division of preventive medicine,brigham and women's hospital and harvard medical school,boston,ma,united states,division of genetics,brigham and women's hospital and harvard medical school,boston,ma, United States, department of public health and clinical medicine,section for nutritional research,umeå university,umeå, Sweden, department of nutrition,harvard school of public health,boston,ma,united states,department of epidemiology,harvard school of public health,boston,ma,united states,channing division of network medicine,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, diabetes and cardiovascular disease - genetic epidemiology,department of clinical sciences,skåne university hospital,lund university,malmö, Sweden, genetic and molecular epidemiology unit,lund university diabetes centre,department of clinical sciences,skåne university hospital,lund university,malmö,sweden,department of public health and clinical medicine,section for medicine,umeå university,umeå,sweden,department of nutrition,harvard school of public health,boston,ma, United States
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Authors
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