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No evidence of a causal association of type 2 diabetes and glucose metabolism with atrial fibrillation.

Citation
Harati, H., et al. “No Evidence Of A Causal Association Of Type 2 Diabetes And Glucose Metabolism With Atrial Fibrillation.”. Diabetologia, pp. 800-804.
Center Stanford University
Author Hadi Harati, Daniela Zanetti, Abhiram Rao, Stefan Gustafsson, Marco Perez, Erik Ingelsson, Joshua W Knowles
Keywords atrial fibrillation, Genome-wide association, Mendelian randomisation, type 2 diabetes
Abstract

AIMS/HYPOTHESIS: Several epidemiological studies have shown an increased risk of atrial fibrillation in individuals with type 2 diabetes or milder forms of dysglycaemia. We aimed to assess whether this relation is causal using a Mendelian randomisation approach.

METHODS: Two-sample Mendelian randomisation was used to obtain estimates of the influence of type 2 diabetes, fasting blood glucose (FBG), and HbA on the risk of atrial fibrillation. Instrumental variables were constructed using available summary statistics from meta-analyses of genome-wide association studies (GWAS) for type 2 diabetes and associated phenotypes. Pleiotropic SNPs were excluded from the analyses. The most recent GWAS meta-analysis summary statistics for atrial fibrillation, which included over 1 million individuals (approximately 60,000 individuals with atrial fibrillation) was used for outcome analysis.

RESULTS: Neither type 2 diabetes (OR 1.01 [95% CI 0.98, 1.03]; p = 0.37), nor FBG (OR 0.95 [95% CI 0.82, 1.09] per mmol/l; p = 0.49) or HbA (OR 1.01 [95% CI, 0.85, 1.17] per mmol/mol [%]; p = 0.88) were associated with atrial fibrillation in Mendelian randomisation analyses. We had >80% statistical power to detect ORs of 1.08, 1.06 and 1.09 or larger for type 2 diabetes, FBG and HbA, respectively, for associations with atrial fibrillation.

CONCLUSIONS/INTERPRETATION: This Mendelian randomisation analysis does not support a causal role of clinical significance between genetically programmed type 2 diabetes, FBG or HbA and development of atrial fibrillation. These data suggest that drug treatment to reduce dysglycaemia is unlikely to be an effective strategy for atrial fibrillation prevention.

DATA AVAILABILITY: The datasets analysed during the current study are available from the following repository: Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al (2018) GWAS summary statistics for AF (N=60,620 AF cases and 970,216 controls). Center for Statistical Genetics: http://csg.sph.umich.edu/willer/public/afib2018/nielsen-thorolfsdottir-….

Year of Publication
2019
Journal
Diabetologia
Volume
62
Issue
5
Number of Pages
800-804
Date Published
12/2019
ISSN Number
1432-0428
DOI
10.1007/s00125-019-4836-y
Alternate Journal
Diabetologia
PMID
30810766
PMCID
PMC6451665
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