基因-生活方式相互作用与 2 型糖尿病：EPIC 相互作用病例-队列研究。
Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.
机构信息
Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
Lund University, Malmö, Sweden; Umeå University, Umeå, Sweden.
出版信息
PLoS Med. 2014 May 20;11(5):e1001647. doi: 10.1371/journal.pmed.1001647. eCollection 2014 May.
BACKGROUND
Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.
METHODS AND FINDINGS
The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50×10-3) and waist circumference (p for interaction = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score.
CONCLUSIONS
The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
背景
对 2 型糖尿病（T2D）的遗传基础的理解已经取得了快速进展，但在具有足够统计效力的研究中，尚未系统地研究常见遗传变异与生活方式风险因素之间的相互作用。因此，我们旨在量化遗传和生活方式因素对 T2D 风险的综合影响，以便为预防策略提供信息。
方法和发现
InterAct 研究包括 12403 例新诊断的 T2D 病例和来自 340234 名欧洲参与者队列的代表性亚队列中的 16154 名个体，随访时间为 399 万人年。我们使用 Prentice 加权 Cox 回归和随机效应荟萃分析方法研究了可加遗传 T2D 风险评分与可修改和不可修改风险因素的综合作用。在年轻个体中，遗传评分的影响明显更大（交互作用的 p 值为 1.20×10-4）。在更瘦的个体中，遗传风险相对较高（每标准偏差[4.4 个风险等位基因]），这一点在体重指数（交互作用的 p 值为 1.50×10-3）和腰围（交互作用的 p 值为 7.49×10-9）方面均如此。按分层分析绝对风险显示肥胖对 T2D 风险的重要性。在正常体重个体中，遗传评分极端四分位数的 T2D 10 年累积发病率从 0.25%上升至 0.89%，而在肥胖个体中从 4.22%上升至 7.99%。我们没有发现遗传评分与性别、糖尿病家族史、体力活动或地中海饮食评分评估的饮食习惯之间存在显著的交互作用。
结论
T2D 遗传风险评分的相对效应在年轻和瘦的参与者中更大。然而，这一亚组的绝对风险较低，因此不是预防干预的合理目标。在任何遗传风险水平下，肥胖所带来的高绝对风险突显了对生活方式干预采取普遍而非有针对性方法的重要性。
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