MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom.
PLoS Med. 2010 Aug 31;7(8):e1000332. doi: 10.1371/journal.pmed.1000332.
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.
我们之前的研究表明，通过全基因组关联研究（GWAS）鉴定的多个遗传基因座以累积的方式增加肥胖的易感性。然而，目前尚不清楚这种遗传易感性是否可以通过积极的生活方式得到减轻，以及减轻的程度如何。我们旨在通过一项基于人群的研究评估积极生活方式对肥胖遗传易感性的影响。
我们在欧洲癌症前瞻性调查（EPIC）-诺福克队列中对 20430 名年龄在 39-79 岁之间的个体（平均随访时间为 3.6 年）的肥胖易感基因座中的 12 个 SNP 进行了基因分型。通过在 12 个 SNP 中累加 BMI 增加的等位基因，为每个个体计算遗传易感性评分。通过自我管理的问卷评估身体活动。使用线性和逻辑回归模型，假设每个 BMI 增加的等位基因具有附加效应，分别检查遗传易感性评分及其与身体活动的相互作用对 BMI/肥胖风险和 BMI 随时间变化的主要影响。每个 BMI 增加的等位基因与 BMI 增加 0.154（标准误差[SE] 0.012）kg/m^2（p = 6.73 x 10^（-37））有关（相当于身高 1.70 米的人体重增加 445 克）。这种关联在不活跃的人群中（0.205 [SE 0.024] kg/m^2 [p = 3.62 x 10^（-18）; 592 g 体重]）比在活跃的人群中更为明显（0.131 [SE 0.014] kg/m^2 [p = 7.97 x 10^（-21）; 379 g 体重]）（p（交互）= 0.005）。同样，每个 BMI 增加的等位基因在整个人群中使肥胖的风险增加 1.116 倍（95%置信区间[CI]为 1.093-1.139，p = 3.37 x 10^（-26）），但在不活跃的个体中明显增加（优势比[OR] = 1.158 [95% CI 1.118-1.199；p = 1.93 x 10^（-16）]）比在活跃的个体中更明显（OR = 1.095（95% CI 1.068-1.123；p = 1.15 x 10^（-12）]）。与横断面观察结果一致，身体活动改变了遗传易感性评分与随访期间 BMI 变化之间的关联（p（交互）= 0.028）。
我们的研究表明，通过积极的生活方式，估计携带 12 个最近通过 GWAS 鉴定的基因座中的任何一个风险等位基因，可使常见肥胖的遗传易感性降低 40%。请稍后在文章中查看编辑摘要。
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