ArticleDiabetes2023
A Guide for Selection of Genetic Instruments in Mendelian Randomization Studies of Type 2 Diabetes and HbA1c: Toward an Integrated Approach.
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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Article
- Anxiety Disorder Types From a Metabolomics Perspective: A Mendelian Randomization Analysis Based on 1400 Plasma Metabolites.Brain and behavior · 2026Article
- Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in schizophrenia.Cell reports. Medicine · 2026Article
- Elucidating the Causal Relationships Between B Cells, Dendritic Cells, and Multiple Sclerosis Pathogenesis.Brain and behavior · 2026Article
- Disentangling the relationship between glucose, insulin and brain health: A UK Biobank study.Diabetes, obesity & metabolism · 2026Article
- Genetic Susceptibility toLife (Basel, Switzerland) · 2026Article
- Knowledge-graph embeddings for osteoarthritis candidate prediction.NPJ digital medicine · 2026Article
- Prospects of Mendelian randomization in hepatology: a comprehensive literature review with practice guidance.Clinical and molecular hepatology · 2025Review
- Causal Associations Between Pre-Pregnancy Diabetes Mellitus and Pre-Eclampsia Risk: Insights from a Mendelian Randomization Study.Healthcare (Basel, Switzerland) · 2025Article
- Therapeutic Target Discovery for Multiple Myeloma: Identifying Druggable Genes via Mendelian Randomization.Biomedicines · 2025Article
- Article
- Unpicking Causal Relationships Between Grip Strength and Cardiorespiratory Fitness: A Bidirectional Mendelian Randomization Study.Scandinavian journal of medicine & science in sports · 2024Article
- Mendelian randomization analysis reveals the combined effects of epigenetics and telomere biology in hematologic cancers.Clinical epigenetics · 2024Article
- Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization.International journal of molecular sciences · 2024Article
- Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank.Journal of medical genetics · 2024Article
- Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study.Cell reports. Medicine · 2024Observational
- A brief comparison of polygenic risk scores and Mendelian randomisation.BMC medical genomics · 2024Article
- Potential causal association of diabetes mellitus and blood glucose related indexes with the onset of epilepsy: a two-sample Mendelian randomization study.Frontiers in neurology · 2024Article
- Genetically proxied inhibition of kidney function pathways and increased risk of type 2 diabetes in Africans: A Mendelian randomization study.Science progressArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
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.
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Registered trials
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.