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

ABSTRACT: 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/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). 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.

SUBMITTER: Li S

PROVIDER: S-EPMC2930873 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Li Shengxu S Zhao Jing Hua JH Luan Jian'an J Ekelund Ulf U Luben Robert N RN Khaw Kay-Tee KT Wareham Nicholas J NJ Loos Ruth J F RJ

PLoS medicine 20100831 8

<h4>Background</h4>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.<h4>Methods and findings</h4>We genotyp ...[more]

PMID: 20824172

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Project description:BackgroundThe European Working Group for Sarcopenia in Older People (EWGSOP) published a case-finding algorithm for sarcopenia, recommending muscle mass measurement in older adults with low grip strength (women <20 kg; men <30 kg) or slow walking speed (?0.8 m/s). However, the implications of adopting this algorithm into clinical practice are unclear. Therefore, we aimed to explore the physical capability of men and women from a British population-based cohort study.MethodsIn the European Prospective Investigation into Cancer-Norfolk study, 8,623 community-based adults (48-92 years old) underwent assessment of grip strength, walking speed, timed chair stands and standing balance. The proportion of older men and women (?65 years) fulfilling EWGSOP criteria for muscle mass measurement was estimated. Additionally, cross-sectional associations of physical capability with age and sex were explored using linear and logistic regression.ResultsApproximately 1 in 4 older participants (28.8%) fulfilled criteria for muscle mass measurement with a greater proportion of women than men falling below threshold criteria (33.6% versus 23.6%). Even after adjustment for anthropometry, women were 12.4 kg (95% Confidence Interval [CI] 12.0, 12.7) weaker, took 12.0% (95% CI 10.0, 14.0) longer to perform five chair stands and were 1.82 (95% CI 1.48, 2.23) times more likely to be unable to hold a tandem stand for 10 seconds than men, although usual walking speed was similar. Physical capability was inversely associated with age and per year, walking speed decreased by 0.01 m/s (95% CI 0.01, 0.01) and grip strength decreased by 0.49 kg (men; 95% CI 0.46, 0.51) and 0.25 kg (women; 95% CI 0.23, 0.27). Despite this, there was still variation within age-groups and not all older people had low physical capability.ConclusionsEvery effort to optimise functional health in later life should be made since poor function is not inevitable. However, if the EWGSOP sarcopenia case-finding algorithm is endorsed, large proportions of older people could qualify for muscle mass measurement which is not commonly available. Considering population ageing, further discussion is needed over the utility of muscle mass measurement in clinical practice.

Project description:BackgroundHeavy drinkers of alcohol are reported to use hospitals more than non-drinkers, but it is unclear whether light-to-moderate drinkers use hospitals more than non-drinkers.ObjectiveWe examined the relationship between alcohol consumption in 10,883 men and 12,857 women aged 40-79 years in the general population and subsequent admissions to hospital and time spent in hospital.MethodsParticipants from the EPIC-Norfolk prospective population-based study were followed for ten years (1999-2009) using record linkage.ResultsCompared to current non-drinkers, men who reported any alcohol drinking had a lower risk of spending more than twenty days in hospital multivariable adjusted OR 0.80 (95%CI 0.68-0.94) after adjusting for age, smoking status, education, social class, body mass index and prevalent diseases. Women who were current drinkers were less likely to have any hospital admissions multivariable adjusted OR 0.84 (95%CI 0.74-0.95), seven or more admissions OR 0.77 (95% CI 0.66-0.88) or more than twenty hospital days OR 0.70 (95%CI 0.62-0.80). However, compared to lifelong abstainers, men who were former drinkers had higher risk of any hospital admissions multivariable adjusted OR 2.22 (95%CI 1.51-3.28) and women former drinkers had higher risk of seven or more admissions OR 1.30 (95%CI 1.01-1.67).ConclusionCurrent alcohol consumption was associated with lower risk of future hospital usage compared with non-drinkers in this middle aged and older population. In men, this association may in part be due to whether former drinkers are included in the non-drinker reference group but in women, the association was consistent irrespective of the choice of reference group. In addition, there were few participants in this cohort with very high current alcohol intake. The measurement of past drinking, the separation of non-drinkers into former drinkers and lifelong abstainers and the choice of reference group are all influential in interpreting the risk of alcohol consumption on future hospitalisation.

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

Publications

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

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