| Title: | Thyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study |
| Journal: | The Journal of Clinical Endocrinology & Metabolism |
| Published: | 6 May 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32374820/ |
| DOI: | https://doi.org/10.1210/clinem/dgaa239 |
| URL: | https://academic.oup.com/jcem/article-pdf/105/8/2634/36842154/dgaa239.pdf |
Publication 13686
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Abstract
CONTEXT: Observational studies suggest that variations in normal range thyroid function are associated with cardiovascular diseases. However, it remains to be determined whether these associations are causal or not.</p>
OBJECTIVE: To test whether genetically determined variation in normal range thyroid function is causally associated with the risk of stroke and coronary artery disease (CAD) and investigate via which pathways these relations may be mediated.</p>
DESIGN, SETTING, AND PARTICIPANTS: Mendelian randomization analyses for stroke and CAD using genetic instruments associated with normal range thyrotropin (TSH) and free thyroxine levels or Hashimoto's thyroiditis and Graves' disease. The potential mediating role of known stroke and CAD risk factors was examined. Publicly available summary statistics data were used.</p>
MAIN OUTCOME MEASURES: Stroke or CAD risk per genetically predicted increase in TSH or FT4 levels.</p>
RESULTS: A 1 standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91-0.99; P = 0.008). Multivariable MR analyses indicated that this effect is mainly mediated via atrial fibrillation. MR analyses did not show a causal association between normal range thyroid function and CAD. Secondary analyses showed a causal relationship between Hashimoto's thyroiditis and a 7% increased risk of CAD (OR, 1.07; 95% CI, 1.01-1.13; P = 0.026), which was mainly mediated via body mass index.</p>
CONCLUSION: These results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke, and CAD. We identify variation in normal range thyroid function and Hashimoto's thyroiditis as risk factors for stroke and CAD, respectively.</p>
20 Keywords
- Adult
- Atrial Fibrillation
- Body Mass Index
- Coronary Artery Disease
- Datasets as Topic
- Female
- Graves Disease
- Hashimoto Disease
- Humans
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Reference Values
- Risk Factors
- Stroke
- Thyroid Function Tests
- Thyroid Gland
- Thyrotropin
- Thyroxine
8 Authors
- Eirini Marouli
- Aleksander Kus
- Fabiola Del Greco M
- Layal Chaker
- Robin Peeters
- Alexander Teumer
- Panos Deloukas
- Marco Medici
1 Application
| Application ID | Title |
|---|---|
| 9922 | Advancing understanding, prediction, prevention and treatment of coronary heart disease through application of genetics to UK Biobank |
Enabling scientific discoveries that improve human health