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

VL - 9

SP - e1003607

JO - P L o S Genetics

JF - P L o S Genetics

SN - 1553-7390

IS - 7

ER -