An Environment-Wide Association Study (EWAS) on type 2 diabetes mellitus.
An Environment-Wide Association Study (EWAS) on type 2 diabetes mellitus.
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DOI：
10.1371/journal.pone.0010746
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发表时间：
2010-05-20
期刊：
影响因子：
3.7
通讯作者：
Butte AJ
中科院分区：
文献类型：
--
作者：
Patel CJ;Bhattacharya J;Butte AJ
2 型糖尿病 (T2D) 和其他慢性疾病是由许多遗传和环境因素的复杂组合引起的。很少有方法可以将特定的物理环境因素与疾病全面联系起来。我们进行了一项试点全环境关联研究（EWAS），其中流行病学数据以类似于全基因组关联研究（GWAS）的方式进行了全面、系统的解释。我们进行了多项横断面分析，将 266 个独特的环境因素与空腹血糖 (FBG) 浓度≥126 mg/dL 定义的 T2D 临床状态联系起来。我们利用了疾病控制中心 (CDC) 国家健康和营养检查调查 (NHANES) 1999 年至 2006 年的队列。队列中的样本数量从 503 到 3,318 不等。逻辑回归模型根据年龄、性别、体重指数（BMI）、种族和社会经济地位（SES）估计进行了调整。与 GWAS 一样，多重比较受到控制，重要的发现得到了其他队列的验证。我们发现农药衍生物七氯环氧化物（暴露量变化 1 SD，调整后 OR 为 1.7；p<0.001）和维生素 γ-生育酚（调整后 OR 1.5；p<0.001）之间存在显着关联。还发现了较高浓度的多氯联苯 (PCB)，例如 PCB170（调整后 OR 2.2；p<0.001）。与 T2D 相关的保护因素包括 β-胡萝卜素（调整后 OR 0.6；p<0.001）。尽管确定因果关系存在困难，但与 T2D 相关的具有重大影响的新因素的潜力证明了使用 EWAS 来创建关于环境对疾病的广泛影响的假设是合理的。即使在这项基于先前收集的流行病学措施的研究中，也可以发现环境因素的影响大小与 GWAS 迄今发现的最佳位点相当。
Type 2 Diabetes (T2D) and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS), in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS). We performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG) concentration ≥126 mg/dL. We utilized available Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI), ethnicity, and an estimate of socioeconomic status (SES). As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p<0.001), and the vitamin γ-tocopherol (adjusted OR 1.5; p<0.001). Higher concentrations of polychlorinated biphenyls (PCBs) such as PCB170 (adjusted OR 2.2; p<0.001) were also found. Protective factors associated with T2D included β-carotenes (adjusted OR 0.6; p<0.001). Despite difficulty in ascertaining causality, the potential for novel factors of large effect associated with T2D justify the use of EWAS to create hypotheses regarding the broad contribution of the environment to disease. Even in this study based on prior collected epidemiological measures, environmental factors can be found with effect sizes comparable to the best loci yet found by GWAS.
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