Evidence mapPaperPMID 36669000Full record

ArticleDiabetes2023

A Guide for Selection of Genetic Instruments in Mendelian Randomization Studies of Type 2 Diabetes and HbA1c: Toward an Integrated Approach.

Victoria Garfield, Antoine Salzmann, Stephen Burgess, Nish Chaturvedi

Abstract read
In one paragraph

Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

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

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Genetic Susceptibility toLife (Basel, Switzerland) · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
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  14. Article
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  17. Observational
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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

4 authors.

Victoria GarfieldMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, U.K.ORCID 0000-0002-5127-0890
Antoine SalzmannMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, U.K.
Stephen BurgessDepartment of Public Health and Primary Care and MRC Biostatistics Unit, University of Cambridge, Cambridge, U.K.
Nish ChaturvediMRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, U.K.

Funding

British Heart Foundation SP/16/6/32726Medical Research Council MC_PC_17228Medical Research Council MC_UU_00002/7Medical Research Council MC_UU_00019/1Wellcome Trust 204623
6 · The paper itself

Abstract

In this study we examine the instrument selection strategies currently used throughout the type 2 diabetes and HbA1c Mendelian randomization (MR) literature. We then argue for a more integrated and thorough approach, providing a framework to do this in the context of HbA1c and diabetes. We conducted a literature search for MR studies that have instrumented diabetes and/or HbA1c. We also used data from the UK Biobank (UKB) (N = 349,326) to calculate instrument strength metrics that are key in MR studies (the F statistic for average strength and R2 for total strength) with two different methods ("individual-level data regression" and Cragg-Donald formula). We used a 157-single nucleotide polymorphism (SNP) instrument for diabetes and a 51-SNP instrument (with partition into glycemic and erythrocytic as well) for HbA1c. Our literature search yielded 48 studies for diabetes and 22 for HbA1c. Our UKB empirical examples showed that irrespective of the method used to calculate metrics of strength and whether the instrument was the main one or included partition by function, the HbA1c genetic instrument is strong in terms of both average and total strength. For diabetes, a 157-SNP instrument was shown to have good average strength and total strength, but these were both substantially lesser than those of the HbA1c instrument. We provide a careful set of five recommendations to researchers who wish to genetically instrument type 2 diabetes and/or HbA1c. In MR studies of glycemia, investigators should take a more integrated approach when selecting genetic instruments, and we give specific guidance on how to do this.

Indexed as

Diabetes Mellitus, Type 2Glycated HemoglobinPolymorphism, Single NucleotideGenome-Wide Association StudyHumansMendelian Randomization AnalysisGlycated Hemoglobin

Identifiers

PMID36669000
PMCPMC7614590

What Socratic holds

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Registered trials

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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.