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

English version České info

Background:
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.

Methods and Findings:
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/m² (p = 6.73×10⁻³⁷) 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/m² [p = 3.62×10⁻¹⁸; 592 g in weight]) than in active people (0.131 [SE 0.014] kg/m² [p = 7.97×10⁻²¹; 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 = 3.37×10⁻²⁶) 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 = 1.93×10⁻¹⁶]) than in active individuals (OR = 1.095 (95% CI 1.068–1.123; p = 1.15×10⁻¹²]). 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).

Conclusions:
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

Vyšlo v časopise: Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study. PLoS Med 7(8): e32767. doi:10.1371/journal.pmed.1000332
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000332

Souhrn

Zdroje

1. PapasMA

AlbergAJ

EwingR

HelzlsouerKJ

GaryTL

2007

The built environment and obesity.

Epidemiol Rev

129

143

2. BouchardC

2008

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

Obesity (Silver Spring)

Suppl 3

S10

3. HillJO

2006

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

Endocr Rev

750

761

4. EkelundU

FranksPW

SharpS

BrageS

WarehamNJ

2007

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

Diabetes Care

2101

2106

5. MaesHH

NealeMC

EavesLJ

1997

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

Behav Genet

325

351

6. FraylingTM

TimpsonNJ

WeedonMN

ZegginiE

FreathyRM

2007

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

Science

316

889

894

7. ScuteriA

SannaS

ChenWM

UdaM

AlbaiG

2007

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

PLoS Genet

e115

doi:10.1371/journal.pgen.0030115

8. LoosRJ

LindgrenCM

LiS

WheelerE

ZhaoJH

2008

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

Nat Genet

768

775

9. WillerCJ

SpeliotesEK

LoosRJ

LiS

LindgrenCM

2009

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

Nat Genet

10. ThorleifssonG

WaltersGB

GudbjartssonDF

SteinthorsdottirV

SulemP

2009

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

Nat Genet

11. LiS

ZhaoJH

LuanJ

LubenRN

RodwellSA

2010

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

Am J Clin Nutr

184

190

12. ManolioTA

CollinsFS

CoxNJ

GoldsteinDB

HindorffLA

2009

Finding the missing heritability of complex diseases.

Nature

461

747

753

13. DayN

OakesS

LubenR

KhawKT

BinghamS

1999

EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer.

Br J Cancer

Suppl 1

103

14. RiboliE

KaaksR

1997

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

Int J Epidemiol

Suppl 1

15. WarehamNJ

JakesRW

RennieKL

SchuitJ

MitchellJ

2003

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.

Public Health Nutr

407

413

16. HinneyA

NguyenTT

ScheragA

FriedelS

BronnerG

2007

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

PLoS ONE

e1361

17. VimaleswaranKS

LiS

ZhaoJH

LuanJ

2009

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

Am J Clin Nutr

425

428

18. RampersaudE

MitchellBD

PollinTI

FuM

ShenH

2008

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

Arch Intern Med

168

1791

1797

19. SonestedtE

RoosC

GullbergB

EricsonU

WirfaltE

2009

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

Am J Clin Nutr

1418

1425

20. AndreasenCH

Stender-PetersenKL

MogensenMS

TorekovSS

WegnerL

2008

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

Diabetes

101

21. CauchiS

StutzmannF

Cavalcanti-ProencaC

DurandE

PoutaA

2009

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

J Mol Med

537

546

22. JonssonA

RenstromF

LyssenkoV

BritoEC

IsomaaB

2009

Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15,925 Swedish and 2,511 Finnish adults.

Diabetologia

1334

1338

23. HakanenM

RaitakariOT

LehtimakiT

PeltonenN

PahkalaK

2009

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

J Clin Endocrinol Metab

1281

1287

24. TanJT

DorajooR

SeielstadM

SimXL

OngRT

2008

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

Diabetes

2851

2857

25. LappalainenTJ

TolppanenAM

KolehmainenM

SchwabU

LindstromJ

2009

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

Obesity (Silver Spring)

832

836

26. McCafferyJM

PapandonatosGD

BondDS

LyonsMJ

WingRR

2009

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

Am J Clin Nutr

1011

1018

27. MustelinL

SilventoinenK

PietilainenK

RissanenA

KaprioJ

2009

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

Int J Obes (Lond)

28. SilventoinenK

HasselbalchAL

LallukkaT

BoglL

PietilainenKH

2009

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

Am J Clin Nutr

1096

1103

29. KarnehedN

TyneliusP

HeitmannBL

RasmussenF

2006

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

Public Health Nutr

851

858

30. LuanJA

WongMY

DayNE

WarehamNJ

2001

Sample size determination for studies of gene-environment interaction.

Int J Epidemiol

1035

1040

31. WongMY

DayNE

LuanJA

ChanKP

WarehamNJ

2003

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

Int J Epidemiol

32. WongMY

DayNE

LuanJA

WarehamNJ

2004

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

Stat Med

987

998

33. KhawKT

JakesR

BinghamS

WelchA

LubenR

2006

Work and leisure time physical activity assessed using a simple, pragmatic, validated questionnaire and incident cardiovascular disease and all-cause mortality in men and women: The European Prospective Investigation into Cancer in Norfolk prospective population study.

Int J Epidemiol

1034

1043

34. BessonH

EkelundU

BrageS

LubenR

BinghamS

2008

Relationship between subdomains of total physical activity and mortality.

Med Sci Sports Exerc

1909