Shengxu Li and colleagues use data from a large prospective observational cohort to examine the extent to which a genetic predisposition toward obesity may be modified by living a physically active lifestyle

A Hinney

A Jonsson

A Scuteri

C Bouchard

CH Andreasen

CJ Willer

E Rampersaud

E Riboli

E Sonestedt

G Thorleifsson

H Besson

HH Maes

JA Luan

Jian'an Luan

Jing Hua Zhao

JM McCaffery

JO Hill

John P. A. Ioannidis

JT Tan

K Silventoinen

Kay-Tee Khaw

KS Vimaleswaran

KT Khaw

L Mustelin

M Hakanen

MA Papas

MY Wong

N Day

N Karnehed

Nicholas J. Wareham

NJ Wareham

RJ Loos

Robert N. Luben

Ruth J. F. Loos

S Cauchi

S Li

Shengxu Li

TA Manolio

TJ Lappalainen

TM Frayling

U Ekelund

Ulf Ekelund

English

PubMed

Crossref

PLoS Medicine

Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study

We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS) increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study. We genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y) from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI)-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error [SE] 0.012) kg/m(2) (p = 6.73 x 10(-37)) increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall). This association was significantly (p(interaction) = 0.005) more pronounced in inactive people (0.205 [SE 0.024] kg/m(2) [p = 3.62 x 10(-18); 592 g in weight]) than in active people (0.131 [SE 0.014] kg/m(2) [p = 7.97 x 10(-21); 379 g in weight]). Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26)) in the whole population, but significantly (p(interaction) = 0.015) more in inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(-16)]) than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1.15 x 10(-12)]). Consistent with the cross-sectional observations, physical activity modified the association between the genetic predisposition score and change in BMI during follow-up (p(interaction) = 0.028). Our study shows that living a physically active lifestyle is associated with a 40% reduction in the genetic predisposition to common obesity, as estimated by the number of risk alleles carried for any of the 12 recently GWAS-identified loci. Please see later in the article for the Editors' Summary

Robert N Luben

Nicholas J Wareham

Ruth J F Loos

Directory of Open Access Journals

Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study.

We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS) increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study. = 0.028).Our study shows that living a physically active lifestyle is associated with a 40% reduction in the genetic predisposition to common obesity, as estimated by the number of risk alleles carried for any of the 12 recently GWAS-identified loci.Please see later in the article for the Editors' Summar

Li Shengxu

Zhao Jing Hua

Luan Jian'an

Ekelund Ulf

Luben Robert N.

Khaw Kay-Tee

Wareham Nicholas J.

Loos Ruth J. F.

Public Library of Science (PLOS)

A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.

Assessing the effect of interaction between an FTO variant (rs9939609) and physical Physical Activity and Genetic Obesity Risk PLoS

Combined effects of MC4R and FTO common genetic variants on obesity in European general populations.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies.

EPIC-Norfolk: study design and characteristics of the cohort.

Estimation of magnitude in gene-environment interactions in the presence of measurement error.

Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity.

Finding the missing heritability of complex diseases.

FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity.

FTO variants are associated with obesity in the Chinese and Malay populations in Singapore.

Gene X environment interaction of vigorous exercise and body mass index among male Vietnam-era twins.

Gene-environment interactions in the etiology of obesity: defining the fundamentals.

Genetic and environmental factors in relative body weight and human adiposity.

Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants.

Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.

Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.

Increase in physical activity energy expenditure is associated with reduced metabolic risk independent of change in fatness and fitness.

Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation.

Modification effects of physical activity and protein intake on heritability of body size and composition.

Physical activity and the association of common FTO gene variants with body mass index and obesity.

Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene.

Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins.

Physical activity, diet and gene-environment interactions in relation to body mass index and waist circumference: the Swedish young male twins study.

Relationship between subdomains of total physical activity and mortality. Med Sci Sports Exerc 40: 1909–1915. Physical Activity and Genetic Obesity Risk PLoS Medicine | www.plosmedicine.org 8

Sample size determination for studies of gene-environment interaction.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

The built environment and obesity.

The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study.

The detection of gene-environment interaction for continuous traits: should we deal with measurement error by bigger studies or better measurement?

The EPIC Project: rationale and study design. European Prospective Investigation into Cancer and Nutrition.

Understanding and addressing the epidemic of obesity: an energy balance perspective.

Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

file:///data/core-remote/dit/data/public_library_of_science/pdf/be0/ZnRwOi8vZnRwLm5jYmkubmxtLm5paC5nb3YvcHViL3BtYy9vYV9wYWNrYWdlL2Y5L2JmL1BNQzI5MzA4NzMudGFyLmd6.pdf

Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study

Abstract

Similar works

Full text

Available Versions

Crossref

Directory of Open Access Journals

Public Library of Science (PLOS)

Public Library of Science (PLOS)