The effect of genetically predicted higher adulthood body mass index on blood pressure traits: A protocol for a systematic review and meta-analysis of Mendelian randomisation studies.

Background: Mendelian randomisation (MR) studies have been used to investigate whether higher body mass index causally influences blood pressure outcomes. However, conclusions vary across studies, potentially reflecting differences in risk of bias, populations and analytical methods. This systematic review aims to synthesise MR evidence on the effect of variation in adulthood body mass index (BMI) on blood pressure outcomes. Methods: We will search three databases (Embase, MEDLINE and Science Citation Index). Two reviewers will independently screen titles and abstracts and full texts for inclusion according to eligibility criteria. Data will be extracted into predefined tables using Microsoft Excel. Risk of bias and certainty of evidence will be assessed using modified risk-of-bias tools and Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE), respectively. The evidence will then be synthesised and presented in figures and tables, as appropriate. The reporting of this systematic review will follow the PRISMA-2020 guidelines. Anticipated findings: By comparing methods and results and potentially meta-analysing results, we will be able to precisely estimate the magnitude and likelihood of the causal effect of adulthood BMI on blood pressure. As well as examining whether the findings are consistent across studies, we will also determine risk of bias for each exposure-outcome pair. We will establish sources of between study heterogeneity. In subsequent work, this systematic review will be triangulated with evidence from randomised controlled trials.