Differentiating Associations of Glycemic Traits With Atherosclerotic and Thrombotic Outcomes: Mendelian Randomization Investigation.
Publication Date
2022-10-01Journal Title
Diabetes
ISSN
0012-1797
Publisher
American Diabetes Association
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Yuan, S., Mason, A. M., Burgess, S., & Larsson, S. C. (2022). Differentiating Associations of Glycemic Traits With Atherosclerotic and Thrombotic Outcomes: Mendelian Randomization Investigation.. Diabetes https://doi.org/10.2337/db21-0905
Abstract
We conducted a Mendelian randomization analysis to differentiate associations of four glycemic indicators with a broad range of atherosclerotic and thrombotic diseases. Independent genetic variants associated with fasting glucose (FG), 2 h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) at the genome-wide significance threshold were used as instrumental variables. Summary-level data for 12 atherosclerotic and 4 thrombotic outcomes were obtained from large genetic consortia and the FinnGen and UK Biobank studies. Higher levels of genetically predicted glycemic traits were consistently associated with increased risk of coronary atherosclerosis-related diseases and symptoms. Genetically predicted glycemic traits except HbA1c showed positive associations with peripheral artery disease risk. Genetically predicted FI levels were positively associated with risk of ischemic stroke and chronic kidney disease. Genetically predicted FG and 2hGlu were positively associated with risk of large artery stroke. Genetically predicted 2hGlu levels showed positive associations with risk of small vessel stroke. Higher levels of genetically predicted glycemic traits were not associated with increased risk of thrombotic outcomes. Most associations for genetically predicted levels of 2hGlu and FI remained after adjustment for other glycemic traits. Increase in glycemic status appears to increase risks of coronary and peripheral artery atherosclerosis but not thrombosis.
Keywords
Atherosclerosis, Blood Glucose, Genome-Wide Association Study, Glycated Hemoglobin, Humans, Insulin, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Stroke
Sponsorship
Wellcome Trust (204623/Z/16/Z)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (MC_UU_00002/7)
National Institute for Health Research (IS-BRC-1215-20014)
Identifiers
External DOI: https://doi.org/10.2337/db21-0905
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337357
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