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

Citation
Harati, Hadi, et al. “No Evidence of a Causal Association of Type 2 Diabetes and Glucose Metabolism With Atrial Fibrillation”. 2019. Diabetologia, vol. 62, no. 5, 2019, 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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