Effects of thyroid function on hemostasis, coagulation, and fibrinolysis: a Mendelian Randomization study

Thyroid ◽  
2021 ◽  
Author(s):  
Christina Ellervik ◽  
Samia Mora ◽  
Aleksander Kuś ◽  
Bjørn Olav Åsvold ◽  
Eirini Marouli ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Mendelian Randomization ◽  
Coagulation And Fibrinolysis

scholarly journals Association of Thyroid Function with Blood Pressure and Cardiovascular Disease: A Mendelian Randomization

2021 ◽  
Vol 11 (12) ◽  
pp. 1306
Author(s):  
Alice Giontella ◽  
Luca A. Lotta ◽  
John D. Overton ◽  
Aris Baras ◽  
Andrea Sartorio ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Thyroid Function ◽  
Lower Risk ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Thyroid Peroxidase ◽  
Genome Wide Association Studies ◽  
Causal Association

Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper- or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), hyper- and hypothyroidism, and anti-thyroid peroxidase antibodies (TPOAb), from genome-wide association studies (GWAS), were selected as MR instrumental variables. SNPs–outcome (BP, CVD) associations were evaluated in a large-scale cohort, the Malmö Diet and Cancer Study (n = 29,298). Causal estimates were computed by inverse-variance weighted (IVW), weighted median, and MR-Egger approaches. Genetically increased levels of TSH were associated with decreased systolic BP and with a lower risk of atrial fibrillation. Hyperthyroidism and TPOAb were associated with a lower risk of atrial fibrillation. Our data support a causal association between genetically decreased levels of TSH and both atrial fibrillation and systolic BP. The lack of significance after Bonferroni correction and the sensitivity analyses suggesting pleiotropy, should prompt us to be cautious in their interpretation. Nevertheless, these findings offer mechanistic insight into the etiology of CVD. Further work into the genes involved in thyroid functions and their relation to cardiovascular outcomes may highlight pathways for targeted intervention.

scholarly journals Mendelian Randomization analyses reveal a causal effect of thyroid function on stroke via atrial fibrillation

2019 ◽  
Author(s):  
Eirini Marouli ◽  
Aleksander Kus ◽  
M. Fabiola Del Greco ◽  
Layal Chaker ◽  
Robin Peeters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Thyroid Function ◽  
Mendelian Randomization ◽  
Normal Range ◽  
Standard Deviation Increase ◽  
Hashimoto’S Disease ◽  
Increased Risk ◽  
Hashimoto's Disease ◽  
Cad Risk

AbstractBackgroundSeveral 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 FindingsWe 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).ConclusionsThese 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.

Mendelian randomization highlights the causal role of normal thyroid function on blood lipid profiles

Endocrinology ◽  
2021 ◽  
Author(s):  
Yanjun Wang ◽  
Ping Guo ◽  
Lu Liu ◽  
Yanan Zhang ◽  
Ping Zeng ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Genetic Correlation ◽  
Thyroid Function ◽  
Observational Studies ◽  
Blood Lipids ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies

Abstract The association between thyroid function and dyslipidemia has been well documented in observational studies. However, observational studies are prone to confounding, making it difficult to conduct causal inference. We performed a two-sample bi-directional Mendelian randomization (MR) using summary statistics from large-scale genome-wide association studies (GWASs) of thyroid stimulating hormone (TSH), free thyroxine (FT4) and blood lipids. We chose inverse variance weighted (IVW) method as main analysis, and consolidated results through various sensitivity analyses involving six different MR methods under different model specifications. We further conducted genetic correlation analysis and colocalization analysis to deeply reflect the causality. The IVW method showed per one standard deviation (SD) increase in normal TSH was significantly associated with a 0.048 SD increase in total cholesterol (TC; P < 0.001) and a 0.032 SD increase in low-density lipoprotein cholesterol (LDL; P = 0.021). Per one SD increase in normal FT4 was significantly associated with a 0.056 SD decrease in TC (P = 0.014) and a 0.072 SD decrease in LDL (P = 0.009). Neither TSH nor FT4 showed causal associations with high-density lipoprotein cholesterol (HDL) and triglycerides (TG). No significant causal effect of blood lipids on normal TSH or FT4 can be detected. All results were largely consistent when using several alternative MR methods, and were re-confirmed by both genetic correlation analysis and colocalization analysis. Our study suggested that even within reference range, higher TSH or lower FT4 are causally associated with increased TC and LDL, while no reverse causal association can be found.

scholarly journals Causal associations of thyroid function and dysfunction with overall, breast and thyroid cancer: A two‐sample Mendelian randomization study

2020 ◽  
Vol 147 (7) ◽  
pp. 1895-1903 ◽  
Author(s):  
Shuai Yuan ◽  
Siddhartha Kar ◽  
Mathew Vithayathil ◽  
Paul Carter ◽  
Amy M. Mason ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Function ◽  
Mendelian Randomization

scholarly journals Thyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study

2020 ◽  
Vol 105 (8) ◽  
pp. 2634-2641 ◽  
Author(s):  
Eirini Marouli ◽  
Aleksander Kus ◽  
Fabiola Del Greco M ◽  
Layal Chaker ◽  
Robin Peeters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Thyroid Function ◽  
Hashimoto’S Thyroiditis ◽  
Mendelian Randomization ◽  
Hashimoto's Thyroiditis ◽  
Normal Range ◽  
Standard Deviation Increase ◽  
Increased Risk ◽  
Cad Risk

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. 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. 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. Main Outcome Measures Stroke or CAD risk per genetically predicted increase in TSH or FT4 levels. 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. 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.

scholarly journals Thyroid Function and Risk of Anemia: A Multivariable-Adjusted and Mendelian Randomization Analysis in the UK Biobank

2021 ◽  
Author(s):  
Nicolien A van Vliet ◽  
Annelies E P Kamphuis ◽  
Wendy P J den Elzen ◽  
Gerard J Blauw ◽  
Jacobijn Gussekloo ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Clinical Diagnosis ◽  
Thyroid Function ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Intracellular Regulation ◽  
Clinical Diagnoses ◽  
The Uk ◽  
Randomization Analysis

Abstract Context Thyroid dysfunction is associated with higher anemia prevalence, although causality remains unclear. Objective This study aimed to investigate the association between thyroid function and anemia. Methods This cross-sectional and Mendelian randomization study included 445 482 European participants from the UK Biobank (mean age 56.77 years (SD 8.0); and 54.2% women). Self-reported clinical diagnosis of hypothyroidism was stated by 21 860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3431 (0.8%). Anemia, defined as hemoglobin level of < 13 g/dL in men and < 12 g/dL in women, was present in 18 717 (4.2%) participants. Results In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12; 95% CI, 1.05-1.19 and OR 1.09; 95% CI, 0.91-1.30), although with wide confidence intervals for hyperthyroidism. We did not observe an association of higher or lower genetically influenced thyrotropin (TSH) with anemia (vs middle tertile: OR for lowest tertile 0.98 [95% CI, 0.95-1.02]; highest tertile 1.02 [95% CI, 0.98-1.06]), nor of genetically influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05; 95% CI, 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes. Conclusion While self-reported clinical diagnosis of hypothyroidism was associated with higher anemia risk, we did not find evidence supporting a causal association with variation of thyroid function within the euthyroid range. However, intracellular regulation of thyroid hormones might play a role in developing anemia.

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