Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3723486?pdf=render |
| _version_ | 1818991415629185024 |
|---|---|
| author | Shafqat Ahmad Gull Rukh Tibor V Varga Ashfaq Ali Azra Kurbasic Dmitry Shungin Ulrika Ericson Robert W Koivula Audrey Y Chu Lynda M Rose Andrea Ganna Qibin Qi Alena Stančáková Camilla H Sandholt Cathy E Elks Gary Curhan Majken K Jensen Rulla M Tamimi Kristine H Allin Torben Jørgensen Soren Brage Claudia Langenberg Mette Aadahl Niels Grarup Allan Linneberg Guillaume Paré InterAct Consortium DIRECT Consortium Patrik K E Magnusson Nancy L Pedersen Michael Boehnke Anders Hamsten Karen L Mohlke Louis T Pasquale Oluf Pedersen Robert A Scott Paul M Ridker Erik Ingelsson Markku Laakso Torben Hansen Lu Qi Nicholas J Wareham Daniel I Chasman Göran Hallmans Frank B Hu Frida Renström Marju Orho-Melander Paul W Franks |
| author_facet | Shafqat Ahmad Gull Rukh Tibor V Varga Ashfaq Ali Azra Kurbasic Dmitry Shungin Ulrika Ericson Robert W Koivula Audrey Y Chu Lynda M Rose Andrea Ganna Qibin Qi Alena Stančáková Camilla H Sandholt Cathy E Elks Gary Curhan Majken K Jensen Rulla M Tamimi Kristine H Allin Torben Jørgensen Soren Brage Claudia Langenberg Mette Aadahl Niels Grarup Allan Linneberg Guillaume Paré InterAct Consortium DIRECT Consortium Patrik K E Magnusson Nancy L Pedersen Michael Boehnke Anders Hamsten Karen L Mohlke Louis T Pasquale Oluf Pedersen Robert A Scott Paul M Ridker Erik Ingelsson Markku Laakso Torben Hansen Lu Qi Nicholas J Wareham Daniel I Chasman Göran Hallmans Frank B Hu Frida Renström Marju Orho-Melander Paul W Franks |
| author_sort | Shafqat Ahmad |
| collection | DOAJ |
| description | 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, age(2), 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. |
| first_indexed | 2024-12-20T20:09:54Z |
| format | Article |
| id | doaj.art-50be97164e0041728ad86db2a7739c06 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T20:09:54Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-50be97164e0041728ad86db2a7739c062022-12-21T19:27:51ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0197e100360710.1371/journal.pgen.1003607Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.Shafqat AhmadGull RukhTibor V VargaAshfaq AliAzra KurbasicDmitry ShunginUlrika EricsonRobert W KoivulaAudrey Y ChuLynda M RoseAndrea GannaQibin QiAlena StančákováCamilla H SandholtCathy E ElksGary CurhanMajken K JensenRulla M TamimiKristine H AllinTorben JørgensenSoren BrageClaudia LangenbergMette AadahlNiels GrarupAllan LinnebergGuillaume ParéInterAct ConsortiumDIRECT ConsortiumPatrik K E MagnussonNancy L PedersenMichael BoehnkeAnders HamstenKaren L MohlkeLouis T PasqualeOluf PedersenRobert A ScottPaul M RidkerErik IngelssonMarkku LaaksoTorben HansenLu QiNicholas J WarehamDaniel I ChasmanGöran HallmansFrank B HuFrida RenströmMarju Orho-MelanderPaul W FranksNumerous 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, age(2), 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.http://europepmc.org/articles/PMC3723486?pdf=render |
| spellingShingle | Shafqat Ahmad Gull Rukh Tibor V Varga Ashfaq Ali Azra Kurbasic Dmitry Shungin Ulrika Ericson Robert W Koivula Audrey Y Chu Lynda M Rose Andrea Ganna Qibin Qi Alena Stančáková Camilla H Sandholt Cathy E Elks Gary Curhan Majken K Jensen Rulla M Tamimi Kristine H Allin Torben Jørgensen Soren Brage Claudia Langenberg Mette Aadahl Niels Grarup Allan Linneberg Guillaume Paré InterAct Consortium DIRECT Consortium Patrik K E Magnusson Nancy L Pedersen Michael Boehnke Anders Hamsten Karen L Mohlke Louis T Pasquale Oluf Pedersen Robert A Scott Paul M Ridker Erik Ingelsson Markku Laakso Torben Hansen Lu Qi Nicholas J Wareham Daniel I Chasman Göran Hallmans Frank B Hu Frida Renström Marju Orho-Melander Paul W Franks Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. PLoS Genetics |
| title | Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. |
| title_full | Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. |
| title_fullStr | Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. |
| title_full_unstemmed | Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. |
| title_short | Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. |
| title_sort | gene physical activity interactions in obesity combined analysis of 111 421 individuals of european ancestry |
| url | http://europepmc.org/articles/PMC3723486?pdf=render |
| work_keys_str_mv | AT shafqatahmad genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT gullrukh genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT tiborvvarga genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT ashfaqali genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT azrakurbasic genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT dmitryshungin genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT ulrikaericson genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT robertwkoivula genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT audreyychu genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT lyndamrose genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT andreaganna genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT qibinqi genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT alenastancakova genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT camillahsandholt genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT cathyeelks genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT garycurhan genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT majkenkjensen genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT rullamtamimi genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT kristinehallin genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT torbenjørgensen genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT sorenbrage genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT claudialangenberg genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT metteaadahl genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT nielsgrarup genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT allanlinneberg genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT guillaumepare genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT interactconsortium genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT directconsortium genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT patrikkemagnusson genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT nancylpedersen genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT michaelboehnke genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT andershamsten genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT karenlmohlke genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT louistpasquale genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT olufpedersen genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT robertascott genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT paulmridker genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT erikingelsson genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT markkulaakso genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT torbenhansen genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT luqi genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT nicholasjwareham genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT danielichasman genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT goranhallmans genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT frankbhu genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT fridarenstrom genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT marjuorhomelander genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry AT paulwfranks genephysicalactivityinteractionsinobesitycombinedanalysisof111421individualsofeuropeanancestry |