遗传关联性研究(genetic association study，GAS)的证据是促进人类基因组计划取得真正进展并最终在医疗和公共卫生实践中进行信息整合的关键。然而，GAS证据等级的优劣评价和证据综合能力一直受到结果报告不规范的限制。加强遗传关联性研究报告质量(Strengthening the Reporting of GAS, STREGA)声明即为旨在加强该类研究报告透明化和提高其报告质量的指南。本文主要介绍STREGA声明的背景和条目清单。
关键词：加强观察性流行病学研究报告质量; 遗传关联性研究; 观察性研究; 报告规范; STROBE; STREGA
一、STREGA背景介绍
遗传关联性研究(genetic association study，GAS)是通过比较病例组和对照组中序列变异的等位基因(或基因型)频率差异来推断基因序列变异与疾病之间关联的研究，是复杂疾病遗传学研究的重要方法之一。
与传统病例对照研究比较，GAS具有较为复杂的基因-基因、基因-环境交互作用的特点，普遍需要多重比较和分层分析，当研究基因数量较大或序列变异点位较多时，还会涉及一些遗传分析专业算法及软件。
随着GAS的迅速发展，如何规范详实地报告研究结果，提高结果可信度与转化率，指导临床实践成为十分重要的问题。鉴于此，2009年Little等在STROBE声明的基础上提出了加强遗传关联性研究报告质量(Strengthening the Reporting of GAS, STREGA)声明。STREGA声明对STROBE清单22项条目中的12项进行了扩展，涉及如研究对象的选择、遗传变异的定义、描述基因型或单倍型的方法、Hardy-Weinberg平衡的应用等GAS中需重点说明的内容。
二、STREGA声明的条目清单
STREGA声明条目清单中英文
| 内容 | 条目序号 | STROBE条目内容 | STREGA条目内容 |
| Title and abstract 题目与摘要 | 1 | a. Indicate the study's design with a commonly used term in the title or the abstract a. 题目或摘要中要有常用专业术语表述研究设计 | |
| b. Provide in the abstract an informative and balanced summary of what was done and what was found b. 摘要内容要丰富，并且能准确地表述研究中做了什么、发现了什么 | |||
| Introduction 前言 | |||
| Background rationale 背景 | 2 | Explain the scientific background and rationale for the investigation being reported 对所报告的研究背景和原理进行解释 | |
| Objectives 目标 | 3 | State specific objectives, including any pre-specified hypotheses 阐明研究目标，包括任何预先确定的假设 | State if the study is the first report of a genetic association, a replication effort or both 说明该研究是首次报告某个遗传关联研究，还是重复研究，或者两者兼有 |
| Methods 方法 | |||
| Study design 研究设计 | 4 | Present key elements of study design early in the paper 在论文中尽早陈述研究设计的要素 | |
| Setting 研究现场 | 5 | Describe the setting, locations and relevant dates, including periods of recruitment, exposure, follow-up and data collection 描述研究现场、具体场所和相关时间范围(包括研究对象征集、暴露、随访和数据收集时间) | |
| Participants 研究对象 | 6 | a. Cohort study—give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up Case-control study—give the eligibility criteria, and the sources and methods of case ascertainment and control selection. Give the rationale for the choice of cases and controls Cross-sectional study—give the eligibility criteria and the sources and methods of selection of participants a. 队列研究—描述选择研究对象的合格标准、人群来源和选择方法；描述随访方法 病例对照研究—描述选择确诊病例和对照的合格标准、人群来源和选择方法；描述选择病例和对照的原理 横断面研究—描述选择研究对象的合格标准、人群来源和选择方法 | Give information on the criteria and methods for selection of subsets of participants from a larger study, when relevant 研究对象来自一个大型研究的一部分时，说明选择参与者的标准和方法 |
| b. Cohort study—for matched studies, give matching criteria and number of exposed and unexposed Case control study—for matched studies, give matching criteria and the number of controls per case b. 队列研究—配对研究描述配对标准和暴露与非暴露数目 病例对照研究—配对研究描述配对标准和每个病例对应的对照数目 | |||
| Variables 研究变量 | 7 | a. Clearly define all outcomes, exposures, predictors, potential confounders and effect modifiers. Give diagnostic criteria, if applicable a. 明确定义结局、暴露、预测因子、潜在的混杂因子和效应修饰因子。如果可能，给出诊断标准 | b. Clearly define genetic exposures (genetic variants) using a widely-used nomenclature system. Identify variables likely to be associated with population stratification (confounding by ethnic origin) b. 需用公认的命名法明确定义遗传暴露(遗传变异)，确定与人群分层(种族混杂)有关的变量 |
| Data sources/ measurement 数据来源/测量 | 8* | a. For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods, if there is more than one group a. 对每个变量，描述其数据来源和详细的判定(测量)方法。如果有多组，还应描述各组之间判定方法的可比性 | b. Describe laboratory methods, including source and storage of DNA, genotyping methods and platforms (including the allele calling algorithm used and its version), error rates and call rates. State the laboratory, centre where genotyping was done. Describe comparability of laboratory methods, if there is more than one group. Specify whether genotypes were assigned using all of the data from the study simultaneously or in smaller batches b. 描述实验方法，包括DNA的来源与保存方法，基因分型方法和平台(包括等位基因判定算法和版本)，错误率和检出率。说明基因分型实验室/中心的名称。如果是多中心实验室，说明不同实验室方法的可比性。说明基因型分配使用的是所有同步研究的数据还是其中一小部分的数据 |
| Bias 偏倚 | 9 | a. Describe any efforts to address potential sources of bias a. 描述减少潜在偏倚的过程 | b. For quantitative outcome variables, specify if any investigation of potential bias resulting from pharmacotherapy was undertaken. If relevant, describe the nature and magnitude of the potential bias and explain what approach was used to deal with this b. 对于定量的结局变量，特别说明是否对药物治疗所导致的潜在偏倚进行调查。必要时描述潜在偏倚的性质、大小，并说明使用了何种控制方法 |
| Study size 样本大小 | 10 | Explain how the study size was arrived at 解释样本大小的确定方法 | |
| QuantitativeVariables定量变量 | 11 | Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why 解释分析中如何处理定量变量。如果可能，描述怎样选择分组及分组原因 | If applicable, describe how effects of treatment were dealt with 如果可能，描述怎样处理治疗效果 |
| Statistical methods 统计学方法 | 12 | a. Describe all statistical methods, including those used to control for confounding a. 描述所有统计方法，包括控制混杂的方法 | State software version used and options (or settings) chosen 说明使用的软件版本和选择的选项(或设置) |
| b. Describe any methods used to examine subgroups and interactions b. 描述亚组和交互作用检查方法 | |||
| c. Explain how missing data were addressed c. 描述缺失值的处理方法 | |||
| d. Cohort study—if applicable, explain how loss to follow-up was addressed Case-control study—if applicable, explain how matching of cases and controls was addressed Cross-sectional study—if applicable, describe analytical methods taking account of sampling strategy d. 队列研究—如果可能，解释失访的处理方法 病例对照研究—如果可能，解释病例和对照的匹配方法 横断面研究—如果可能，描述根据抽样策略确定的统计方法 | |||
| e. Describe any sensitivity analyses e. 描述敏感性分析 | |||
| f.State whether Hardy-Weinberg equilibrium was considered and, if so, how f. 说明是否考虑了哈迪温伯格平衡，如果考虑，说明是如何分析的 | |||
| g. Describe any methods used for inferring genotypes or haplotypes g. 描述所有用于推测基因型或者单倍型的方法 | |||
| h. Describe any methods used to assess or address population stratification h. 描述所有用于评价或者阐述人群分层的方法 | |||
| i. Describe any methods used to address multiple comparisons or to control risk of false positive findings i. 描述所有用于阐述多重比较或者控制假阳性结果的方法 | |||
| j. Describe any methods used to address and correct for rel latedness among subjects j. 描述所有用于阐述和调整研究对象间关联性的方法 | |||
| Results 结果 | |||
| Participants 研究对象 | 13* | a. Report the numbers of individuals at each stage of the study-e.g., numbers potentially eligible, examined for eligiblity, confirmed eligible, included in the study, completing follow-up and analysed a. 报告研究的各个阶段研究对象的数量，如可能合格的数量、被检验是否合格的数量、证实合格的数量、纳入研究的数量、完成随访的数量和分析的数量 | Report numbers of individuals in whom genotyping was attempted and numbers of individuals in whom genotyping was successful 报告拟进行基因分型的人数和基因分型成功的人数 |
| b. Give reasons for non-participation at each stage b. 描述各个阶段研究对象退出的原因 | |||
| c. Consider use of a flow diagram c. 考虑使用流程图 | |||
| Descriptive data 描述性资料 | 14* | a. Give characteristics of study participants (e.g., demographic, clinical, social) and information on exposures and potential confounders a. 描述研究对象的特征(如人口学、临床和社会特征)以及关于暴露和潜在混杂因子的信息 | Consider giving information by genotype 考虑按基因型提供信息 |
| b. Indicate the number of participants with missing data for each variable of interest b. 指出每个变量存在缺失值的研究对象数目 | |||
| c. Cohort study—summarize follow-up time, e.g. average and total amount c. 队列研究—总结随访时间(如平均时间、总和时间) | |||
| Outcome data 结局资料 | 15* | Cohort study—report numbers of outcome events or summary measures over time 队列研究—报告发生结局事件的数量或人时综合指标 | Report outcomes (phenotypes) for each genotype category over time 按基因型分类报告发生结局事件(变量)随时间的变化 |
| Case-control study—report numbers in each exposure category or summary measures of exposure 病例对照研究—报告各个暴露类别的数量或暴露综合指标 | Report numbers in each genotype category 按基因型分类报告数量 | ||
| Cross-sectional study—report numbers of outcome events or summary measures 横断面研究——报告结局事件的数量或相关综合指标 | Report outcomes (phenotypes) for each genotype category 按基因型分类报告结局事件(表型) | ||
| Main results 主要结果 | 16 | a. Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (e.g., 95% confidence intervals). Make clear which confounders were adjusted for and why they were included a. 给出未校正的和校正混杂因子的关联强度估计值、精确度(如95% CI)。闸明根据哪些混杂因子进行调整以及选择这些因子的原因 | |
| b. Report category boundaries when continuous variables were categorized b. 当对连续性变量分组时报告分组界值 | |||
| c. If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period c. 如果有关联，可将有意义时期内的相对危险度转换成绝对危险度 | |||
| d. Report results of any adjustments for multiple comparisons d. 报告多重比较调整后的结果 | |||
| Other analyses 其他分析 | 17 | a. Report other analyses performed--e.g., analyses of subgroups and interactions and sensitivity analyses a. 报告进行的其他分析，如亚组和交互作用分析、敏感性分析 | |
| b. If numerous genetic exposures (genetic variants) were examined, summarize results from all analyses undertaken b. 如果检测到大量的基因暴露(遗传变异)，总结所有分析的结果 | |||
| c. If detailed results are available elsewhere, state how they can be accessed c. 如果在其他地方有更详细的结果，说明获取的途径 | |||
| Discussion 讨论 | |||
| Key results 重要结果 | 18 | Summarize key results with reference to study objectives 概括与研究假设有关的重要结果 | |
| Limitations 局限性 | 19 | Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias 结合潜在偏倚和不精确的来源，讨论研究的局限性。讨论潜在偏倚的方向和大小 | |
| Interpretation 解释 | 20 | Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies and other relevant evidence 结合研究目的、局限性、多重比较、类似研究的结果和其他相关证据，谨慎给出一个总体的结果解释 | |
| Generalizability 可推广性 | 21 | Discuss the generalizability (external validity) of the study results 讨论研究结果的可推广性(外部真实性) | |
| Other information 其他信息 | |||
| Funding 资助 | 22 | Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based 给出当前研究的资助来源和资助者。如果可能，给出原始研究的资助情况 | |
*病例对照研究中分别给出病例组和对照组的相应信息，队列研究和横断面研究里分别给出暴露组和未暴露组的相应信息
三、注意事项
STREGA声明旨在加强GAS的透明化报告，研究者、审稿人和编辑都可以采用。研究者可以参考STREGA声明撰写论文框架和相应条目细节；审稿人和编辑可参考STREGA声明评价文章的规范性，但STREGA声明不可作为论文真实价值的评判标准。实际应用中，若按照STREGA声明各条目撰写论文，可能导致文章篇幅过长，则应描述清楚重点条目，其他内容可在需要的时候将其作为附加材料提交。
注：本文内容是参考相关文献后对STREGA声明原文的概述，仅代表本网站观点。关于STREGA声明的更多内容详见官方网站(http://www.strobe-statement.org)或Julian Little等发表的论文“STrengthening the REporting of Genetic Association Studies (STREGA): an extension of the STROBE statement (https://pubmed.ncbi.nlm.nih.gov/19192942/)”。
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