| Title: | Fetuin-A and its genetic association with cardiometabolic disease |
| Journal: | Scientific Reports |
| Published: | 6 Dec 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38052855/ |
| DOI: | https://doi.org/10.1038/s41598-023-48600-9 |
| URL: | https://www.nature.com/articles/s41598-023-48600-9.pdf |
Publication 9213
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Abstract
Fetuin-A acts as both an inhibitor of calcification and insulin signaling. Previous studies reported conflicting results on the association between fetuin-A and cardiometabolic diseases. We aim to provide further insights into the association between genetically predicted levels of fetuin-A and cardiometabolic diseases using a Mendelian randomization strategy. Genetic variants associated with fetuin-A and their effect sizes were obtained from previous genetic studies. A series of two-sample Mendelian randomization analyses in 412,444 unrelated individuals from the UK Biobank did not show evidence for an association of genetically predicted fetuin-A with any stroke, ischemic stroke, or myocardial infarction. We do find that increased levels of genetically predicted fetuin-A are associated with increased risk of type 2 diabetes (OR = 1.21, 95%CI 1.13-1.30, P = < 0.01). Furthermore, genetically predicted fetuin-A increases the risk of coronary artery disease in individuals with type 2 diabetes, but we did not find evidence for an association between genetically predicted fetuin-A and coronary artery disease in those without type 2 diabetes (P for interaction = 0.03). One SD increase in genetically predicted fetuin-A decreases risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men (P for interaction = < 0.01). Genetically predicted fetuin-A is associated with type 2 diabetes. Furthermore, type 2 diabetes status modifies the association of genetically predicted fetuin-A with coronary artery disease, indicating that fetuin-A increases risk in individuals with type 2 diabetes. Finally, higher genetically predicted fetuin-A reduces the risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men.</p>
8 Authors
- Lawien Al Ali
- Yordi J. van de Vegte
- M. Abdullah Said
- Hilde E. Groot
- Tom Hendriks
- Ming Wai Yeung
- Erik Lipsic
- Pim van der Harst
1 Application
| Application ID | Title |
|---|---|
| 15031 | Genetic dissection of cardiovascular risk factors and their relation to disease to establish causality and identify novel targets of therapy |
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