Developing cross-population Mendelian randomization for generalizing evidence ondrug targets: the MRC Cross-Population Mendelian Randomization Network

开发跨人群孟德尔随机化以概括药物靶点证据：MRC 跨人群孟德尔随机化网络

• 批准号: MC_PC_21018
• 负责人: George Davey Smith
• 金额: $ 15.15万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_21018
• 关键词: Developing; cross; population; Mendelian; randomization

The overarching aim of the MRC Cross-Population Mendelian Randomization Network is to integrate research expertise and resources across four MRC Units with expertise in cross-population genetic epidemiology to explore the use of Medelian randomization (MR) to evaluate generalisability of existing drugs and target drugs to specific sub-populations. The network will implement pilot studies focused on specific established drug targets (e.g. CETP, HMGCR) to investigate how differences in genetic architecture between populations affect estimates of efficacy. In parallel we will explore how differences in environmental interactions between populations (including public health policy such as folate supplementation) alter MR estimates of efficacy of such supplementation (using MTHFR as the instrument). The network will focus on the development of both cross-ancestry and ancestry-specific genetic instruments for MR and investigate how genetic colocalization with molecular targets (metabolomic, proteomic and transcriptomic) vary across populations.

MRC跨人群孟德尔随机化网络的总体目标是整合具有跨人群遗传流行病学专业知识的四个MRC单位的研究专门知识和资源，以探索使用麦德林随机化(MR)来评估现有药物和目标药物对特定亚群的普适性。该网络将针对特定的既定药物靶点(如CETP、HMGCR)进行试点研究，以调查不同人群之间的遗传结构差异如何影响疗效估计。同时，我们将探索人群之间环境相互作用的差异(包括叶酸补充等公共卫生政策)如何改变MR对此类补充效果的估计(使用MTHFR作为工具)。该网络将专注于开发用于MR的交叉祖先和祖先特定的遗传工具，并调查与分子靶标(代谢组、蛋白质组和转录组)的遗传共定位如何在不同种群之间变化。