Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.

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Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. / Ahmad, Shafqat; Rukh, Gull; V Varga, Tibor; Ali, Ashfaq; Kurbasic, Azra; Shungin, Dmitry; Ericson, Ulrika; Koivula, Robert; Chu, Audrey Y; Rose, Lynda M; Ganna, Andrea; Qi, Qibin; Stančáková, Alena; Sandholt, Camilla H; Elks, Cathy E; Curhan, Gary; Jensen, Majken K; Tamimi, Rulla M; Allin, Kristine H; Jørgensen, Torben; Brage, Soren; Langenberg, Claudia; Aadahl, Mette; Grarup, Niels; Linneberg, Allan; Paré, Guillaume; Magnusson, Patrik K E; Pedersen, Nancy L; Boehnke, Michael; Hamsten, Anders; Mohlke, Karen L; Pasquale, Louis T; Pedersen, Oluf; Scott, Robert A; Ridker, Paul M; Ingelsson, Erik; Laakso, Markku; Hansen, Torben; Qi, Lu; Wareham, Nicholas J; Chasman, Daniel I; Hallmans, Göran; Hu, Frank B; Renström, Frida; Orho-Melander, Marju; Franks, Paul.

In: PLoS Genetics, Vol. 9, No. 7, e1003607, 2013.

Research output: Contribution to journalArticle

Harvard

Ahmad, S, Rukh, G, V Varga, T, Ali, A, Kurbasic, A, Shungin, D, Ericson, U, Koivula, R, Chu, AY, Rose, LM, Ganna, A, Qi, Q, Stančáková, A, Sandholt, CH, Elks, CE, Curhan, G, Jensen, MK, Tamimi, RM, Allin, KH, Jørgensen, T, Brage, S, Langenberg, C, Aadahl, M, Grarup, N, Linneberg, A, Paré, G, Magnusson, PKE, Pedersen, NL, Boehnke, M, Hamsten, A, Mohlke, KL, Pasquale, LT, Pedersen, O, Scott, RA, Ridker, PM, Ingelsson, E, Laakso, M, Hansen, T, Qi, L, Wareham, NJ, Chasman, DI, Hallmans, G, Hu, FB, Renström, F, Orho-Melander, M & Franks, P 2013, 'Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.', PLoS Genetics, vol. 9, no. 7, e1003607. https://doi.org/10.1371/journal.pgen.1003607

APA

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Ahmad S, Rukh G, V Varga T, Ali A, Kurbasic A, Shungin D, Ericson U, Koivula R, Chu AY, Rose LM, Ganna A, Qi Q, Stančáková A, Sandholt CH, Elks CE, Curhan G, Jensen MK, Tamimi RM, Allin KH, Jørgensen T, Brage S, Langenberg C, Aadahl M, Grarup N, Linneberg A, Paré G, Magnusson PKE, Pedersen NL, Boehnke M, Hamsten A, Mohlke KL, Pasquale LT, Pedersen O, Scott RA, Ridker PM, Ingelsson E, Laakso M, Hansen T, Qi L, Wareham NJ, Chasman DI, Hallmans G, Hu FB, Renström F, Orho-Melander M, Franks P. 2013. Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. PLoS Genetics. 9(7). https://doi.org/10.1371/journal.pgen.1003607

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Ahmad, Shafqat ; Rukh, Gull ; V Varga, Tibor ; Ali, Ashfaq ; Kurbasic, Azra ; Shungin, Dmitry ; Ericson, Ulrika ; Koivula, Robert ; Chu, Audrey Y ; Rose, Lynda M ; Ganna, Andrea ; Qi, Qibin ; Stančáková, Alena ; Sandholt, Camilla H ; Elks, Cathy E ; Curhan, Gary ; Jensen, Majken K ; Tamimi, Rulla M ; Allin, Kristine H ; Jørgensen, Torben ; Brage, Soren ; Langenberg, Claudia ; Aadahl, Mette ; Grarup, Niels ; Linneberg, Allan ; Paré, Guillaume ; Magnusson, Patrik K E ; Pedersen, Nancy L ; Boehnke, Michael ; Hamsten, Anders ; Mohlke, Karen L ; Pasquale, Louis T ; Pedersen, Oluf ; Scott, Robert A ; Ridker, Paul M ; Ingelsson, Erik ; Laakso, Markku ; Hansen, Torben ; Qi, Lu ; Wareham, Nicholas J ; Chasman, Daniel I ; Hallmans, Göran ; Hu, Frank B ; Renström, Frida ; Orho-Melander, Marju ; Franks, Paul. / Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. In: PLoS Genetics. 2013 ; Vol. 9, No. 7.

RIS

TY - JOUR

T1 - Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.

AU - Ahmad, Shafqat

AU - Rukh, Gull

AU - V Varga, Tibor

AU - Ali, Ashfaq

AU - Kurbasic, Azra

AU - Shungin, Dmitry

AU - Ericson, Ulrika

AU - Koivula, Robert

AU - Chu, Audrey Y

AU - Rose, Lynda M

AU - Ganna, Andrea

AU - Qi, Qibin

AU - Stančáková, Alena

AU - Sandholt, Camilla H

AU - Elks, Cathy E

AU - Curhan, Gary

AU - Jensen, Majken K

AU - Tamimi, Rulla M

AU - Allin, Kristine H

AU - Jørgensen, Torben

AU - Brage, Soren

AU - Langenberg, Claudia

AU - Aadahl, Mette

AU - Grarup, Niels

AU - Linneberg, Allan

AU - Paré, Guillaume

AU - Magnusson, Patrik K E

AU - Pedersen, Nancy L

AU - Boehnke, Michael

AU - Hamsten, Anders

AU - Mohlke, Karen L

AU - Pasquale, Louis T

AU - Pedersen, Oluf

AU - Scott, Robert A

AU - Ridker, Paul M

AU - Ingelsson, Erik

AU - Laakso, Markku

AU - Hansen, Torben

AU - Qi, Lu

AU - Wareham, Nicholas J

AU - Chasman, Daniel I

AU - Hallmans, Göran

AU - Hu, Frank B

AU - Renström, Frida

AU - Orho-Melander, Marju

AU - Franks, Paul

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1003607

DO - 10.1371/journal.pgen.1003607

M3 - Article

VL - 9

JO - PLoS Genetics

T2 - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7404

IS - 7

M1 - e1003607

ER -