Reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank: a meta-epidemiological study

OBJECTIVES: To identify whether Mendelian randomisation (MR) studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them.

DESIGN: Cross-sectional meta-epidemiological study.

DATA SOURCES: Web of Science, EMBASE, PubMed and PsycINFO were searched on 15 July 2022 for literature.

ELIGIBILITY CRITERIA: Full research articles that conducted an MR analysis exclusively using individual-level UK Biobank data to obtain a causal estimate of the exposure-outcome relationship (for no more than ten exposures or outcomes).

METHODS AND ANALYSIS: Data were extracted using a 25-item checklist relating to reporting and methodological quality (based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines and the guidelines for performing MR investigations). Article characteristics, such as 2021 Journal Impact Factor, publication year, journal word limit/recommendation, whether the MR analysis was the primary analysis, open access status and whether reporting guidelines were followed, were also extracted. Descriptive statistics were calculated for each item, and whether article characteristics predicted overall article completeness was investigated with linear regression.

RESULTS: 116 articles were included in this review. The proportion of articles which reported complete information/adequate methodology ranged from 3% to 100% across the different items. Palindromic variants, variant replication, missing data, associations of the instrumental variable with the exposure or outcome and bias introduced by two-sample methods used on a single sample were often not completely addressed (<11%). There was no clear evidence that article characteristics predicted overall completeness except for primary analysis status.

CONCLUSIONS: The results identify areas in which the reporting and conducting of MR studies needs to be improved and also suggest researchers do not make use of supplementary materials to sufficiently report secondary analyses. Future research should focus on the quality of code and analyses, attempt direct replications and investigate the impact of the STROBE-MR specifically.

STUDY REGISTRATION: https://osf.io/nwrdj.