Item No.
货号

Section
部分

Checklist item
清单项目

Page No.
页码

Relevant text from manuscript
手稿中的相关文字

1

TITLE and ABSTRACT
标题和摘要

Indicate Mendelian randomization (MR) as the study’s design in the title and/or the abstract if that is a main purpose of the study
如果这是研究的主要目的，请在标题和/或摘要中注明孟德尔随机化(MR)作为研究的设计

Causal relationships between mitochondrial proteins and digestive tract cancer: a bidirectional mendelian randomization study
线粒体蛋白与消化道癌症之间的因果关系：双向孟德尔随机化研究

INTRODUCTION

2

Background
背景

Explain the scientific background and rationale for the reported study. What is the exposure? Is a potential causal relationship between exposure and outcome plausible? Justify why MR is a helpful method to address the study question
解释所报告研究的科学背景和基本原理。什么是曝光？暴露与结果之间是否存在潜在因果关系？证明为什么 MR 是解决研究问题的有效方法

3

Objectives
目标

State specific objectives clearly, including pre-specified causal hypotheses (if any). State that MR is a method that, under specific assumptions, intends to estimate causal effects
明确陈述具体目标，包括预先指定的因果假设（如果有）。说明 MR 是一种在特定假设下估计因果效应的方法

METHODS

4

Study design and data sources
研究设计和数据来源

Present key elements of the study design early in the article. Consider including a table listing sources of data for all phases of the study. For each data source contributing to the analysis, describe the following: 
在文章的前面介绍了研究设计的关键要素。考虑包含一个表格，列出研究所有阶段的数据来源。对于有助于分析的每个数据源，请描述以下内容：

a)
一个）

Setting: Describe the study design and the underlying population, if possible. Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection, when available.
设置：如果可能的话，描述研究设计和潜在人群。描述环境、地点和相关日期，包括招募、接触、随访和数据收集的时期（如果有）。

b)

Participants: Give the eligibility criteria, and the sources and methods of selection of participants. Report the sample size, and whether any power or sample size calculations were carried out prior to the main analysis
参与者：给出参与者的资格标准、选择的来源和方法。报告样本量，以及在主要分析之前是否进行了功效或样本量计算 

c)

Describe measurement, quality control and selection of genetic variants
描述遗传变异的测量、质量控制和选择

d)

For each exposure, outcome, and other relevant variables, describe methods of assessment and diagnostic criteria for diseases
对于每种暴露、结果和其他相关变量，描述疾病的评估方法和诊断标准

e)

Provide details of ethics committee approval and participant informed consent, if relevant
提供伦理委员会批准和参与者知情同意的详细信息（如果相关）

5

Assumptions
假设

Explicitly state the three core IV assumptions for the main analysis (relevance, independence and exclusion restriction) as well assumptions for any additional or sensitivity analysis
明确说明主要分析的三个核心 IV 假设（相关性、独立性和排除限制）以及任何附加分析或敏感性分析的假设

6

Statistical methods: main analysis
统计方法：主要分析

Describe statistical methods and statistics used
描述统计方法和使用的统计数据

a)
一个）

Describe how quantitative variables were handled in the analyses (i.e., scale, units, model)
描述分析中如何处理定量变量（即规模、单位、模型）

b)

Describe how genetic variants were handled in the analyses and, if applicable, how their weights were selected
描述在分析中如何处理遗传变异，以及如何选择其权重（如果适用）

c)

Describe the MR estimator (e.g. two-stage least squares, Wald ratio) and related statistics. Detail the included covariates and, in case of two-sample MR, whether the same covariate set was used for adjustment in the two samples
描述 MR 估计器（例如两阶段最小二乘法、Wald 比）和相关统计数据。详细说明所包含的协变量，以及在两个样本 MR 的情况下，是否使用相同的协变量集在两个样本中进行调整

d)

Explain how missing data were addressed
解释如何解决缺失数据的问题

e)

If applicable, indicate how multiple testing was addressed
如果适用，请说明如何解决多重测试

7

Assessment of assumptions
假设评估

Describe any methods or prior knowledge used to assess the assumptions or justify their validity
描述用于评估假设或证明其有效性的任何方法或先验知识 

8

Sensitivity analyses and additional analyses
敏感性分析和附加分析

Describe any sensitivity analyses or additional analyses performed (e.g. comparison of effect estimates from different approaches, independent replication, bias analytic techniques, validation of instruments, simulations)
描述所进行的任何敏感性分析或附加分析（例如，比较不同方法的效果估计、独立复制、偏差分析技术、仪器验证、模拟）

9

Software and pre-registration
软件和预注册

a)
一个）

Name statistical software and package(s), including version and settings used 
统计软件和软件包的名称，包括所使用的版本和设置

b)

State whether the study protocol and details were pre-registered (as well as when and where)
说明研究方案和详细信息是否预先注册（以及时间和地点）

RESULTS

10

Descriptive data
描述性数据

a)
一个）

Report the numbers of individuals at each stage of included studies and reasons for exclusion. Consider use of a flow diagram
报告纳入研究的每个阶段的人数以及排除的原因。考虑使用流程图

b)

Report summary statistics for phenotypic exposure(s), outcome(s), and other relevant variables (e.g. means, SDs, proportions)
报告表型暴露、结果和其他相关变量（例如平均值、 SD 、比例）的汇总统计数据

c)

If the data sources include meta-analyses of previous studies, provide the assessments of heterogeneity across these studies
如果数据源包括先前研究的荟萃分析，请提供这些研究的异质性评估

d)

For two-sample MR
对于两个样本 MR:

i.  Provide justification of the similarity of the genetic variant-exposure associations between the exposure and outcome samples
。提供暴露样本和结果样本之间遗传变异-暴露关联的相似性的理由

ii.  Provide information on the number of individuals who overlap between the exposure and outcome studies
二.提供有关暴露研究和结果研究之间重叠的个体数量的信息

11

Main results
主要成果

a)
一个）

Report the associations between genetic variant and exposure, and between genetic variant and outcome, preferably on an interpretable scale
报告遗传变异与暴露之间以及遗传变异与结果之间的关联，最好是在可解释的范围内

b)

Report MR estimates of the relationship between exposure and outcome, and the measures of uncertainty from the MR analysis, on an interpretable scale, such as odds ratio or relative risk per SD difference
在可解释的范围内报告暴露与结果之间关系的 MR 估计，以及 MR 分析的不确定性度量，例如比值比或每SD差异的相对风险

c)

If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period
如果相关，请考虑将相对风险的估计转化为有意义的时间段内的绝对风险

d)

Consider plots to visualize results (e.g. forest plot, scatterplot of associations between genetic variants and outcome versus between genetic variants and exposure)
考虑绘制可视化结果的图（例如森林图、遗传变异和结果之间的关联散点图以及遗传变异和暴露之间的关联散点图）

12

Assessment of assumptions
假设评估

a)
一个）

Report the assessment of the validity of the assumptions
报告假设有效性的评估

b)

Report any additional statistics (e.g., assessments of heterogeneity across genetic variants, such as I², Q statistic or E-value)
报告任何其他统计数据（例如，跨遗传变异的异质性评估，例如² 、Q 统计量或 E 值）

13

Sensitivity analyses and additional analyses
敏感性分析和附加分析

a)
一个）

Report any sensitivity analyses to assess the robustness of the main results to violations of the assumptions
报告任何敏感性分析，以评估主要结果对违反假设的稳健性

b)

Report results from other sensitivity analyses or additional analyses
报告其他敏感性分析或附加分析的结果

c)

Report any assessment of direction of causal relationship (e.g., bidirectional MR)
报告对因果关系方向的任何评估（例如双向 MR）

d)

When relevant, report and compare with estimates from non-MR analyses
相关时，报告并与非 MR 分析的估计值进行比较

e)

Consider additional plots to visualize results (e.g., leave-one-out analyses)
考虑额外的图来可视化结果（例如，留一分析）

DISCUSSION

14

Key results 
主要成果

Summarize key results with reference to study objectives
参考研究目标总结主要结果

15

Limitations
局限性

Discuss limitations of the study, taking into account the validity of the IV assumptions, other sources of potential bias, and imprecision. Discuss both direction and magnitude of any potential bias and any efforts to address them
讨论该研究的局限性，同时考虑 IV 假设的有效性、潜在偏差的其他来源和不精确性。讨论任何潜在偏见的方向和程度以及解决这些偏见的任何努力 

16

Interpretation
解释

a)
一个）

Meaning: Give a cautious overall interpretation of results in the context of their limitations and in comparison with other studies
意义：在其局限性的背景下并与其他研究进行比较，对结果给出谨慎的总体解释

b)

Mechanism: Discuss underlying biological mechanisms that could drive a potential causal relationship between the investigated exposure and the outcome, and whether the gene-environment equivalence assumption is reasonable. Use causal language carefully, clarifying that IV estimates may provide causal effects only under certain assumptions
机制：讨论可能驱动所研究的暴露与结果之间潜在因果关系的潜在生物学机制，以及基因-环境等效性假设是否合理。谨慎使用因果语言，澄清 IV 估计仅在某些假设下才可能提供因果效应

c)

Clinical relevance: Discuss whether the results have clinical or public policy relevance, and to what extent they inform effect sizes of possible interventions
临床相关性：讨论结果是否具有临床或公共政策相关性，以及它们在多大程度上告知可能干预措施的效果大小

17

Generalizability 
普遍性 

Discuss the generalizability of the study results (a) to other populations, (b) across other exposure periods/timings, and (c) across other levels of exposure
讨论研究结果 (a) 对其他人群、(b) 其他暴露周期/时间以及 (c) 其他暴露水平的普遍性

OTHER INFORMATION
其他信息

18

Funding
资金

Describe sources of funding and the role of funders in the present study and, if applicable, sources of funding for the databases and original study or studies on which the present study is based
描述资金来源和资助者在本研究中的作用，以及（如果适用）数据库和原始研究或本研究所基于的研究的资金来源

19

Data and data sharing 
数据与数据共享

Provide the data used to perform all analyses or report where and how the data can be accessed, and reference these sources in the article. Provide the statistical code needed to reproduce the results in the article, or report whether the code is publicly accessible and if so, where
提供用于执行所有分析或报告可以在何处以及如何访问数据的数据，并在文章中引用这些来源。提供重现文章中结果所需的统计代码，或报告该代码是否可公开访问，如果可以，则在哪里

20

Conflicts of Interest  
利益冲突

All authors should declare all potential conflicts of interest
所有作者均应声明所有潜在的利益冲突