| 2. |
- Larsson, Susanna C., et al.
(författare)
-
Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases : A Mendelian Randomization Study
- 2019
-
Ingår i: Circulation. - 2574-8300. ; 12:3, s. 121-126
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subclinical thyroid dysfunction, defined as thyroidstimulating hormone levels outside the reference range with normal free thyroxine levels in asymptomatic patients, is associated with alterations in cardiac hemodynamics. We used Mendelian randomization to assess the role of thyroid dysfunction for cardiovascular disease (CVD).METHODS: Single-nucleotide polymorphisms associated with thyroid function were identified from a genome-wide association meta-analysis in up to 72 167 individuals. Data for genetic associations with CVD were obtained from meta-analyses of genome-wide association studies of atrial fibrillation (n= 537 409 individuals), coronary artery disease (n= 184 305 individuals), and ischemic stroke (n= 438 847) as well as from the UK Biobank (n= 367 703 individuals).RESULTS: Genetically predicted thyroid-stimulating hormone levels and hyperthyroidism were statistically significantly associated with atrial fibrillation but no other CVDs at the Bonferroni-corrected level of significance (P< 7.8x10-4). The odds ratios of atrial fibrillation were 1.15 (95% CI, 1.11-1.19; P= 2.4x10-14) per genetically predicted 1 SD decrease in thyroid-stimulating hormone levels and 1.05 (95% CI, 1.03-1.08; P= 5.4x10-5) for genetic predisposition to hyperthyroidism. Genetically predicted free thyroxin levels were not statistically significantly associated with any CVD.CONCLUSIONS: This Mendelian randomization study supports evidence for a causal association of decreased thyroid-stimulating hormone levels in the direction of a mild form of hyperthyroidism with an increased risk of atrial fibrillation but no other CVDs.
|
|
| 3. |
- Yuan, Shuai, et al.
(författare)
-
Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases : A Mendelian Randomisation Study
- 2019
-
Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:12
-
Tidskriftsartikel (refereegranskat)abstract
- Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMp1usC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes Delta 5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma alpha-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma alpha-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.
|
|
