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

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; 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; InterAct Consortium

doi:10.1371/journal.pgen.1003607

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

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 JørgensenSoren Brage, Claudia Langenberg, Mette Aadahl, Niels Grarup, Allan Linneberg, Guillaume Paré, 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, InterAct Consortium

132 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	P L o S Genetics (Online)
Vol/bind	9
Udgave nummer	7
Sider (fra-til)	e1003607
ISSN	1553-7404
DOI	https://doi.org/10.1371/journal.pgen.1003607
Status	Udgivet - jul. 2013

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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., ... InterAct Consortium (2013). Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. P L o S Genetics (Online), 9(7), e1003607. https://doi.org/10.1371/journal.pgen.1003607

Ahmad, S, Rukh, G, Varga, TV, Ali, A, Kurbasic, A, Shungin, D, Ericson, U, Koivula, RW, 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, PW & InterAct Consortium 2013, 'Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry', P L o S Genetics (Online), bind 9, nr. 7, s. e1003607. https://doi.org/10.1371/journal.pgen.1003607

@article{857b56759a324840b4174e46f7ee0b86,

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

abstract = "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.",

author = "Shafqat Ahmad and Gull Rukh and Varga, {Tibor V} and Ashfaq Ali and Azra Kurbasic and Dmitry Shungin and Ulrika Ericson and Koivula, {Robert W} and Chu, {Audrey Y} and Rose, {Lynda M} and Andrea Ganna and Qibin Qi and Alena Stan{\v c}{\'a}kov{\'a} and Sandholt, {Camilla H} and Elks, {Cathy E} and Gary Curhan and Jensen, {Majken K} and Tamimi, {Rulla M} and Allin, {Kristine H} and Torben J{\o}rgensen and Soren Brage and Claudia Langenberg and Mette Aadahl and Niels Grarup and Allan Linneberg and Guillaume Par{\'e} and Magnusson, {Patrik K E} and Pedersen, {Nancy L} and Michael Boehnke and Anders Hamsten and Mohlke, {Karen L} and Pasquale, {Louis T} and Oluf Pedersen and Scott, {Robert A} and Ridker, {Paul M} and Erik Ingelsson and Markku Laakso and Torben Hansen and Lu Qi and Wareham, {Nicholas J} and Chasman, {Daniel I} and G{\"o}ran Hallmans and Hu, {Frank B} and Frida Renstr{\"o}m and Marju Orho-Melander and Franks, {Paul W} and {InterAct Consortium}",

year = "2013",

month = jul,

doi = "10.1371/journal.pgen.1003607",

language = "English",

volume = "9",

pages = "e1003607",

journal = "P L o S Genetics (Online)",

issn = "1553-7404",

publisher = "Public Library of Science",

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TY - JOUR

T1 - Gene × physical activity interactions in obesity

T2 - combined analysis of 111,421 individuals of European ancestry

AU - Ahmad, Shafqat

AU - Rukh, Gull

AU - Varga, Tibor V

AU - Ali, Ashfaq

AU - Kurbasic, Azra

AU - Shungin, Dmitry

AU - Ericson, Ulrika

AU - Koivula, Robert W

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 W

AU - InterAct Consortium

PY - 2013/7

Y1 - 2013/7

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 - Journal article

C2 - 23935507

SN - 1553-7404

VL - 9

SP - e1003607

JO - P L o S Genetics (Online)

JF - P L o S Genetics (Online)

IS - 7

ER -

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

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