Evidence map›Paper›PMID 39407214›Full record

ReviewBMC medicine2024

Common pitfalls in drug target Mendelian randomization and how to avoid them.

Dipender Gill, Marie-Joe Dib, Héléne T Cronjé, Ville Karhunen, Benjamin Woolf, Eloi Gagnon, Iyas Daghlas, Michael Nyberg, Donald Drakeman, Stephen Burgess

Abstract readReview
In one paragraph

Review in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. Low Cholesterol due to APOB Variants: Exploring the Balance Between Liver and Cardiovascular Risk.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  15. Article
  16. Repurposing dipeptidyl peptidase-4 inhibitor for Parkinson's disease prevention: A drug-target Mendelian randomization study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Dipender GillSequoia Genetics, London, UK. dipender.gill@sequoiagenetics.com.
Marie-Joe DibCardiovascular Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Héléne T CronjéSequoia Genetics, London, UK.
Ville KarhunenSequoia Genetics, London, UK.
Benjamin WoolfMedical Research Council Biostatistics Unit, University of Cambridge, Cambridge, UK.
Eloi GagnonCentre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Québec, Canada.
Iyas DaghlasDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Michael NybergCardiovascular Biology, Global Drug Discovery, Novo Nordisk A/S, Maaloev, Denmark.
Donald DrakemanUniversity of Cambridge Centre for Health Leadership & Enterprise, Judge Business School, Trumpington Street, Cambridge, UK.
Stephen BurgessSequoia Genetics, London, UK.

Funding

Medical Research Council MC_UU_00002/7Wellcome Trust 225790
6 · The paper itself

Abstract

backgroundDrug target Mendelian randomization describes the use of genetic variants as instrumental variables for studying the effects of pharmacological agents. The paradigm can be used to inform on all aspects of drug development and has become increasingly popular over the last decade, particularly given the time- and cost-efficiency with which it can be performed even before commencing clinical studies. MAIN BODY: In this review, we describe the recent emergence of drug target Mendelian randomization, its common pitfalls, how best to address them, as well as potential future directions. Throughout, we offer advice based on our experiences on how to approach these types of studies, which we hope will be useful for both practitioners and those translating the findings from such work.

conclusionsDrug target Mendelian randomization is nuanced and requires a combination of biological, statistical, genetic, epidemiological, clinical, and pharmaceutical expertise to be utilized to its full potential. Unfortunately, these skillsets are relatively infrequently combined in any given study.

Indexed as

Mendelian Randomization AnalysisDrug DevelopmentGenetic VariationHumansDrug developmentDrug targetMendelian randomizationPharmacology

Identifiers

PMID39407214
PMCPMC11481744

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.