Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases.
Circulation. Genomic and precision medicine
Lippincott Williams & Wilkins Ltd.
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Larsson, S. C., Allara, E., Mason, A., Michaëlsson, K., & Burgess, S. (2019). Thyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases.. Circulation. Genomic and precision medicine, 12 (3), e002468. https://doi.org/10.1161/circgen.118.002468
Background Subclinical thyroid dysfunction, defined as thyroid-stimulating hormone (TSH) 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. 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 cardiovascular disease 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 TSH levels and hyperthyroidism were statistically significantly associated with atrial fibrillation but no other cardiovascular diseases at the Bonferroni-corrected level of significance (P <7.810-4). The odds ratios of atrial fibrillation were 1.15 (95% confidence interval 1.11-1.19, P=2.410-14) per genetically predicted one standard deviation decrease in TSH levels and 1.05 (95% confidence interval 1.03-1.08, P=5.410-5) for genetic predisposition to hyperthyroidism. Genetically predicted free thyroxin levels were not statistically significantly associated with any cardiovascular disease. Conclusions: This Mendelian randomization study supports evidence for a causal association of decreased TSH levels in the direction of a mild form of hyperthyroidism with increased risk of atrial fibrillation but no other cardiovascular diseases.
Thyroid Gland, Humans, Cardiovascular Diseases, Atrial Fibrillation, Hyperthyroidism, Genetic Predisposition to Disease, Thyrotropin, Thyroxine, Odds Ratio, Polymorphism, Single Nucleotide, Databases, Factual, Genome-Wide Association Study
Wellcome Trust (204623/Z/16/Z)
British Heart Foundation (RG/13/13/30194)
Medical Research Council (MC_UU_00002/7)
British Heart Foundation (RG/18/13/33946)
External DOI: https://doi.org/10.1161/circgen.118.002468
This record's URL: https://www.repository.cam.ac.uk/handle/1810/289337