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Cumulative Effect of Common Genetic Variants Predicts Incident Type 2 Diabetes: A Study of 21,183 Subjects from Three Large Prospective Cohorts 常见遗传变异的累积效应预测2型糖尿病的发生:一项来自三个大型前瞻性队列的21,183名受试者的研究
Pub Date : 2011-11-01 DOI: 10.4172/2161-1165.1000108
Jingyun Yang, Jinying Zhao
Recent genome-wide association studies (GWAS) and their meta-analyses have identified multiple genetic loci that are associated with type 2 diabetes (T2D). Except for variants in the TCF7L2 gene which had a modest effect on diabetic risk, most genetic variants identified so far have only a weak association with diabetes. It is possible that the combination of multiple variants may have a larger effect on disease risk and improve risk prediction. In this study, we focus on SNPs that had been robustly replicated in previous GWAS and were also genotyped in a large sample of 21,183 participants from three large prospective cohorts, including Atherosclerosis Risk in Communities (ARIC) Study, Framingham Offspring Study (FOS) and Multi-Ethnic Study of Atherosclerosis (MESA). Among these, we were able to successfully confirm the associations of 12 SNPs with baseline prevalent T2D in these two cohorts. A genotype risk score (GRS) using these12 risk variants was constructed to examine whether GRS predicts incident diabetes. In a combined meta-analysis, subjects in the highest tertile of GRS had a 1.62-fold increased risk of incident T2D (95% CI, 1.08–2.44, P=1.5×10−14) compared to those in the lowest tertile of GRS after adjustment for age, sex, race, smoking, body mass index (BMI), lipids (HDL and LDL) and systolic blood pressure. Moreover, GRS significantly improves risk prediction and reclassification in T2D beyond known risk factors.
最近的全基因组关联研究(GWAS)及其荟萃分析已经确定了与2型糖尿病(T2D)相关的多个遗传位点。除了TCF7L2基因的变异对糖尿病风险有一定影响外,迄今为止发现的大多数遗传变异与糖尿病只有微弱的关联。多种变异的组合可能对疾病风险有更大的影响,并改善风险预测。在这项研究中,我们重点研究了在以前的GWAS中得到充分复制的snp,并在来自三个大型前瞻性队列的21,183名参与者的大样本中进行了基因分型,包括社区动脉粥样硬化风险(ARIC)研究、Framingham后代研究(FOS)和多种族动脉粥样硬化研究(MESA)。其中,我们能够成功地确认这两个队列中12个snp与基线流行T2D的关联。使用这12个风险变异构建基因型风险评分(GRS)来检验GRS是否能预测糖尿病的发生。在一项综合荟萃分析中,在调整了年龄、性别、种族、吸烟、体重指数(BMI)、血脂(HDL和LDL)和收缩压后,与GRS最低分位数的受试者相比,GRS最高分位数的受试者发生T2D的风险增加了1.62倍(95% CI, 1.08-2.44, P=1.5×10−14)。此外,在已知危险因素之外,GRS显著提高了T2D的风险预测和重新分类。
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引用次数: 3
Utilization of the National Health and Nutrition Examination (NHANES) Survey for Symptoms, Tests, and Diagnosis of Chronic Respiratory Diseases and Assessment of Second hand Smoke Exposure. 利用国家健康和营养检查(NHANES)调查慢性呼吸系统疾病的症状、测试和诊断以及评估二手烟暴露。
Pub Date : 2011-10-01 Epub Date: 2011-10-25 DOI: 10.4172/2161-1165.1000104
Tulay Koru-Sengul, John D Clark, Manuel A Ocasio, Adam Wanner, Lora E Fleming, David J Lee

Background: Respiratory diseases encompass a number of complex disorders that constitute a major cause of both morbidity and mortality worldwide with a major burden to the afflicted as well as the health care systems that care for them. Although the prevalence of chronic respiratory diseases (CRDs) has been decreasing in industrialized countries due to a decreasing number of smokers and stricter laws aimed at reducing exposure to secondhand smoke (SHS), the burden of CRDs in developing world populations is expected to worsen due to communicable disease prevention programs, aging populations, environmental air pollution, and continued tobacco smoke exposure. Although tobacco smoking has been shown to be significantly associated with many CRDs, evidence linking SHS exposure to different CRDs is mixed, especially with low levels of SHS exposure.

Methods: The National Health and Nutrition Examination Survey (NHANES) is a series of studies designed to assess the health and nutritional status of non-institutionalized adults and children in the United States (U.S.). In addition to being used to monitor the health of the U.S. population, NHANES data allow for research into prevalent health problems and their risk factors in the population, such with CRDs and SHS exposure. NHANES data can be utilized to explore a variety of issues related to the assessment of SHS exposure and its association to respiratory symptoms and illnesses.

Results: First, we provide a brief review of NHANES including its strengths and limitations. We then provide a summary of the variables and publically available population based data that can be used to study associations between SHS exposure and CRD symptoms, testing and diagnoses.

Conclusion: Rich and cost effective, NHANES data provide a unique opportunity for research into the risk factors for CRDs in the U.S. population, particularly into the possible health effects of low levels of SHS exposure.

背景:呼吸系统疾病包括许多复杂的疾病,它们构成了世界范围内发病率和死亡率的主要原因,给患者以及照顾他们的卫生保健系统造成了重大负担。尽管由于吸烟者数量的减少和旨在减少二手烟暴露的更严格的法律,慢性呼吸系统疾病(CRDs)的患病率在工业化国家一直在下降,但由于传染病预防计划、人口老龄化、环境空气污染和持续的烟草烟雾暴露,发展中国家人口的CRDs负担预计会恶化。尽管吸烟已被证明与许多慢性致病性疾病显著相关,但将SHS暴露于不同慢性致病性疾病之间联系起来的证据却参差不一,尤其是在低水平SHS暴露情况下。方法:国家健康和营养检查调查(NHANES)是一系列旨在评估美国非机构成人和儿童健康和营养状况的研究。除了用于监测美国人口的健康之外,NHANES数据还允许对人群中普遍存在的健康问题及其风险因素进行研究,例如CRDs和SHS暴露。NHANES数据可用于探讨与评估SHS暴露及其与呼吸道症状和疾病的关系有关的各种问题。结果:首先,我们简要回顾了NHANES,包括它的优势和局限性。然后,我们总结了变量和可公开获得的基于人群的数据,这些数据可用于研究SHS暴露与CRD症状、检测和诊断之间的关系。结论:NHANES数据丰富且具有成本效益,为研究美国人群中CRDs的风险因素,特别是低水平SHS暴露可能对健康的影响提供了独特的机会。
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引用次数: 4
Matching on Race and Ethnicity in Case-Control Studies as a Means of Control for Population Stratification. 病例对照研究中种族和民族匹配作为人口分层的控制手段。
Pub Date : 2011-09-29 DOI: 10.4172/2161-1165.1000101
Anand P Chokkalingam, Melinda C Aldrich, Karen Bartley, Ling-I Hsu, Catherine Metayer, Lisa F Barcellos, Joseph L Wiemels, John K Wiencke, Patricia A Buffler, Steve Selvin

Some investigators argue that controlling for self-reported race or ethnicity, either in statistical analysis or in study design, is sufficient to mitigate unwanted influence from population stratification. In this report, we evaluated the effectiveness of a study design involving matching on self-reported ethnicity and race in minimizing bias due to population stratification within an ethnically admixed population in California. We estimated individual genetic ancestry using structured association methods and a panel of ancestry informative markers, and observed no statistically significant difference in distribution of genetic ancestry between cases and controls (P=0.46). Stratification by Hispanic ethnicity showed similar results. We evaluated potential confounding by genetic ancestry after adjustment for race and ethnicity for 1260 candidate gene SNPs, and found no major impact (>10%) on risk estimates. In conclusion, we found no evidence of confounding of genetic risk estimates by population substructure using this matched design. Our study provides strong evidence supporting the race- and ethnicity-matched case-control study design as an effective approach to minimizing systematic bias due to differences in genetic ancestry between cases and controls.

一些研究人员认为,在统计分析或研究设计中控制自我报告的种族或民族,足以减轻人口分层的不必要影响。在本报告中,我们评估了一项研究设计的有效性,该研究设计涉及对自我报告的种族和种族进行匹配,以最大限度地减少加州种族混合人口中人口分层造成的偏见。我们使用结构化关联方法和一组祖先信息标记估计个体遗传祖先,观察到病例和对照组之间遗传祖先分布无统计学显著差异(P=0.46)。西班牙裔的分层也显示了类似的结果。在对1260个候选基因snp进行人种和民族调整后,我们评估了遗传祖先的潜在混淆,发现对风险估计没有重大影响(>10%)。总之,我们没有发现使用这种匹配设计的种群亚结构混淆遗传风险估计的证据。我们的研究提供了强有力的证据,支持种族和民族匹配的病例对照研究设计是一种有效的方法,可以最大限度地减少病例和对照组之间遗传血统差异造成的系统偏差。
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引用次数: 10
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Epidemiology (Sunnyvale, Calif.)
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