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

Research output: Contribution to journalArticle

111 Citations (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, 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.

Original languageEnglish (US)
Article numbere1003607
JournalPLoS Genetics
Volume9
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

physical activity
obesity
ancestry
Obesity
gene
Meta-Analysis
Genes
meta-analysis
genes
loci
Logistic Models
Genome-Wide Association Study
North America
Sample Size
Multicenter Studies
Single Nucleotide Polymorphism
Linear Models
Alleles
analysis
logistics

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Ahmad, S., Rukh, G., Varga, T. V., Ali, A., Kurbasic, A., Shungin, D., ... Franks, P. W. (2013). Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry. PLoS Genetics, 9(7), [e1003607]. https://doi.org/10.1371/journal.pgen.1003607

Gene × Physical Activity Interactions in Obesity : Combined Analysis of 111,421 Individuals of European Ancestry. / Ahmad, Shafqat; Rukh, Gull; Varga, Tibor V.; Ali, Ashfaq; Kurbasic, Azra; Shungin, Dmitry; Ericson, Ulrika; Koivula, Robert W.; 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 W.

In: PLoS Genetics, Vol. 9, No. 7, e1003607, 07.2013.

Research output: Contribution to journalArticle

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 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
Ahmad, Shafqat ; Rukh, Gull ; Varga, Tibor V. ; Ali, Ashfaq ; Kurbasic, Azra ; Shungin, Dmitry ; Ericson, Ulrika ; Koivula, Robert W. ; 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 W. / Gene × Physical Activity Interactions in Obesity : Combined Analysis of 111,421 Individuals of European Ancestry. In: PLoS Genetics. 2013 ; Vol. 9, No. 7.
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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, 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.",
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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

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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.

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AU - Orho-Melander, Marju

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