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...

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Main Authors:	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.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723486/

id	pubmed-3723486
recordtype	oai_dc
spelling	pubmed-37234862013-08-09 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. Research Article 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. Public Library of Science 2013-07-25 /pmc/articles/PMC3723486/ /pubmed/23935507 http://dx.doi.org/10.1371/journal.pgen.1003607 Text en © 2013 Ahmad et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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.
spellingShingle	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
author_facet	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.
author_sort	Ahmad, Shafqat
title	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_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_sort	gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of european ancestry
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, 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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723486/
_version_	1611997923680190464

Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry

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