Mendelian Randomization analyses reveal a causal effect of thyroid function on stroke via atrial fibrillation
Background: Several observational studies suggest that variations in thyroid function, even within the normal range, are a risk factor for cardiovascular diseases, but it remains to be determined if these associations are causal or not. This study investigates whether the relationship between variation in normal range thyroid function, as well as hypothyroidism and hyperthyroidism, and the risk of stroke and Coronary Artery Disease (CAD) are causal and via which pathways these relations are mediated. Methods and Findings: We performed Mendelian Randomization (MR) analyses for stroke and CAD using genetic instruments associated with TSH and FT4 levels respectively within either the normal range, hypothyroidism or hyperthyroidism. In detected associations, the potential mediatory role of known stroke and CAD risk factors was also examined. A one standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (OR=0.95, 95% CI= 0.91 to 0.99). Multivariable MR analyses indicated that this effect is mediated through atrial fibrillation (AF). Hashimoto's Disease (HD) was associated with a 7% increased risk of CAD (OR=1.07, 95% CI= 1.01 to 1.13). The effect of Hashimoto's Disease (HD) on CAD risk appears to be mediated via body mass index (BMI). Conclusions: These results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke and CAD. Specifically, we identify normal range TSH levels and HD as potential modifiable risk factors for stroke and CAD, respectively.
- Downloaded 263 times
- Download rankings, all-time:
- Site-wide: 96,379
- In genetics: 4,276
- Year to date:
- Site-wide: 98,427
- Since beginning of last month:
- Site-wide: 104,365
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!