A systematic review of the reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank

Background Mendelian randomisation (MR) is a method of causal inference that uses genetic variation as an instrumental variable (IV) to account for confounding. While the number of MR articles published each year is rapidly rising (partly due to large cohort studies such as the UK Biobank making it easier to conduct MR), it is not currently known whether these studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them. Methods We conducted a systematic review of reporting and analysis quality of MR studies using only individual level data from the UK biobank to calculate a causal estimate. We reviewed 64 eligible articles on a 25-item checklist (based on the STROBE-MR reporting guidelines and the Guidelines for performing Mendelian Randomisation investigations). Information on article type and journal information was also extracted. Results Overall, the proportion of articles which reported complete information ranged from 2% to 100% across the different items. Palindromic variants, variant replication, missing data, associations between the IV and variables of exposure/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 Journal Impact Factor, word limit/recommendation or year of publication predicted percentage of article completeness (for the eligible analyses) across items, but there was evidence that whether the MR analyses were primary, joint-primary or secondary analyses did predict completeness. Conclusions The results identify areas in which the reporting and conducting of MR studies needs to be improved and highlights that this is independent of Journal Impact Factor, year of publication or word limits/recommendations. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement MJG, AC and MRM are supported by the Medical Research Council Integrative Epidemiology Unit (MC\_UU\_00011/7). FS, JNK and RCR are supported by a Cancer Research UK programme grant (the Integrative Cancer Epidemiology Programme C18281/A29019). RCR is a de Pass Vice Chancellors Research Fellow at the University of Bristol. The funders had no role in the study design, collection or analysis of data, or interpretation of results. The views expressed in this article are those of the authors and not necessarily any funder or acknowledged person/institution. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data is available via the University of Bristol online data repository and on as well as in Supplementary Table S4.