Giontella Alice, Lotta Luca A, Overton John D, Baras Aris, Sartorio Andrea, Minuz Pietro, Gill Dipender, Melander Olle, Fava Cristiano
Department of Medicine, University of Verona, 37134 Verona, Italy.
Clinical Research Center, Department of Clinical Sciences, Lund University, 214 28 Malmö, Sweden.
J Pers Med. 2021 Dec 6;11(12):1306. doi: 10.3390/jpm11121306.
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.
甲状腺功能对心脏代谢系统具有广泛影响。然而，亚临床甲状腺功能亢进或减退以及甲状腺激素与血压（BP）和心血管疾病（CVD）之间的因果关联尚不清楚。我们旨在通过两样本孟德尔随机化（MR）研究对此进行调查。从全基因组关联研究（GWAS）中选择与促甲状腺激素（TSH）、游离甲状腺素（FT4）、甲状腺功能亢进和减退以及抗甲状腺过氧化物酶抗体（TPOAb）相关的单核苷酸多态性（SNP）作为MR工具变量。在大规模队列马尔默饮食与癌症研究（n = 29,298）中评估SNP与结局（BP、CVD）的关联。通过逆方差加权（IVW）、加权中位数和MR-Egger方法计算因果估计值。遗传上TSH水平升高与收缩压降低以及房颤风险降低相关。甲状腺功能亢进和TPOAb与房颤风险降低相关。我们的数据支持遗传上TSH水平降低与房颤和收缩压之间存在因果关联。Bonferroni校正后缺乏显著性以及敏感性分析表明存在多效性，这应促使我们在解释时保持谨慎。尽管如此，这些发现为CVD的病因提供了机制性见解。对参与甲状腺功能的基因及其与心血管结局的关系进行进一步研究可能会突出靶向干预的途径。
