标题： 孟德尔随机化在多族裔世界中的应用：反思与实用建议 显示英文标题

标题： Mendelian randomization in a multi-ancestry world: reflections and practical advice

摘要： 许多孟德尔随机化（MR）论文仅在欧洲血统的人群中进行，这限制了结果在全局人群中的可转移性。 将MR扩展到多样化的血统群体对于确保公平的生物医学见解至关重要，但带来了分析和概念上的挑战。 本综述考察了在仅限欧洲背景之外进行MR分析的实际挑战，包括使用多血统、不匹配血统和混合人口的数据。 我们解释了在不同人群中MR估计值的明显异质性可能源于遗传变异频率和相关模式的差异，以及表型变量分布的差异，这使得检测因果途径中的真实差异变得复杂。 我们总结了在使用有限的血统特异性数据时选择遗传工具和进行分析的已发表策略，并讨论了在每种情况下纳入不同血统人群外部数据所需的假设。 我们得出结论，应谨慎解释按血统群体划分的MR估计值差异，并考虑这些差异可能由于社会和文化因素而产生。 需要证实生物学机制改变因果途径的证据，以支持不同血统群体之间因果途径存在差异的结论。 显示英文摘要

摘要： Many Mendelian randomization (MR) papers have been conducted only in people of European ancestry, limiting transportability of results to the global population. Expanding MR to diverse ancestry groups is essential to ensure equitable biomedical insights, yet presents analytical and conceptual challenges. This review examines the practical challenges of MR analyses beyond the European only context, including use of data from multi-ancestry, mismatched ancestry, and admixed populations. We explain how apparent heterogeneity in MR estimates between populations can arise from differences in genetic variant frequencies and correlation patterns, as well as from differences in the distribution of phenotypic variables, complicating the detection of true differences in the causal pathway. We summarize published strategies for selecting genetic instruments and performing analyses when working with limited ancestry-specific data, discussing the assumptions needed in each case for incorporating external data from different ancestry populations. We conclude that differences in MR estimates by ancestry group should be interpreted cautiously, with consideration of how the identified differences may arise due to social and cultural factors. Corroborating evidence of a biological mechanism altering the causal pathway is needed to support a conclusion of differing causal pathways between ancestry groups.