Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Association of thyroid function with blood pressure and cardiovascular disease : A mendelian randomization

Giontella, Alice LU orcid ; Lotta, Luca A. ; Overton, John D. ; Baras, Aris ; Sartorio, Andrea ; Minuz, Pietro ; Gill, Dipender ; Melander, Olle LU orcid and Fava, Cristiano LU (2021) In Journal of Personalized Medicine 11(12).
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular diseases, Genetics, Hypertension, Mendelian randomization, Polymorphisms, Thyroid
in
Journal of Personalized Medicine
volume
11
issue
12
article number
1306
publisher
MDPI AG
external identifiers
  • pmid:34945778
  • scopus:85121579763
ISSN
2075-4426
DOI
10.3390/jpm11121306
language
English
LU publication?
yes
id
af6363d6-fa47-41e1-adcb-5067f4c3210e
date added to LUP
2022-10-14 15:02:57
date last changed
2024-06-13 20:11:01
@article{af6363d6-fa47-41e1-adcb-5067f4c3210e,
  abstract     = {{<p>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.</p>}},
  author       = {{Giontella, Alice and Lotta, Luca A. and Overton, John D. and Baras, Aris and Sartorio, Andrea and Minuz, Pietro and Gill, Dipender and Melander, Olle and Fava, Cristiano}},
  issn         = {{2075-4426}},
  keywords     = {{Cardiovascular diseases; Genetics; Hypertension; Mendelian randomization; Polymorphisms; Thyroid}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{MDPI AG}},
  series       = {{Journal of Personalized Medicine}},
  title        = {{Association of thyroid function with blood pressure and cardiovascular disease : A mendelian randomization}},
  url          = {{http://dx.doi.org/10.3390/jpm11121306}},
  doi          = {{10.3390/jpm11121306}},
  volume       = {{11}},
  year         = {{2021}},
}