Genetic Thyrotropin Regulation of Atrial Fibrillation Risk Is Mediated Through an Effect on Height.

Atrial Fibrillation / genetics Blood Pressure / genetics Body Height / genetics Genetic Predisposition to Disease / genetics Genome-Wide Association Study Heart Disease Risk Factors Humans Mendelian Randomization Analysis Polymorphism, Single Nucleotide Thyroid Function Tests Thyroid Gland / metabolism Thyrotropin / blood
atrial fibrillation height mendelian randomization thyrotropin

Journal

The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362

Informations de publication

Date de publication:
16 06 2021
Historique:
received: 02 12 2020
revised: 31 03 2021
pubmed: 26 4 2021
medline: 5 10 2021
entrez: 25 4 2021
Statut: ppublish

Résumé

A genetic predisposition to lower thyrotropin (TSH) levels is associated with increased atrial fibrillation (AF) risk through undefined mechanisms. Defining the genetic mediating mechanisms could lead to improved targeted therapies to mitigate AF risk. We used 2-sample mendelian randomization (MR) to test associations between TSH-associated single-nucleotide variations and 16 candidate mediators. We then performed multivariable mendelian randomization (MVMR) to test for a significant attenuation of the genetic association between TSH and AF, after adjusting for each mediator significantly associated with TSH. Four candidate mediators (free thyroxine, systolic blood pressure, heart rate, and height) were significantly inversely associated with genetically predicted TSH after adjusting for multiple testing. In MVMR analyses, adjusting for height significantly decreased the magnitude of the association between TSH and AF from -0.12 (SE 0.02) occurrences of AF per SD change in height to -0.06 (0.02) (P = .005). Adjusting for the other candidate mediators did not significantly attenuate the association. The genetic association between TSH and increased AF risk is mediated, in part, by taller stature. Thus, some genetic mechanisms underlying TSH variability may contribute to AF risk through mechanisms determining height occurring early in life that differ from those driven by thyroid hormone-level elevations in later life.

Identifiants

DOI: 10.1210/clinem/dgab272 PMID: 33895829 PMC: PMC8208678
pubmed: 33895829
pii: 6250092
doi: 10.1210/clinem/dgab272
pmc: PMC8208678
doi:

Substances chimiques

Thyrotropin 9002-71-5

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2124-2132

Subventions

Organisme : NIH HHS
ID : S10 OD017985
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007569
Pays : United States
Organisme : NHLBI NIH HHS
ID : U19 HL065962
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025141
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142856
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 16FTF30130005
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD074711
Pays : United States
Organisme : NIGMS NIH HHS
ID : RC2 GM092618
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM115305
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD043483
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006378
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM130791
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024975
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS032830
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004798
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Mingjian Shi (M)

Department of Biomedical Informatics & Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
ORCID: 0000-0003-1569-9822

Ali M Manouchehri (AM)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Christian M Shaffer (CM)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Nataraja Sarma Vaitinadin (NS)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Jacklyn N Hellwege (JN)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Joe-Elie Salem (JE)

Département de Pharmacologie, APHP, Sorbonne Université, INSERM, UNICO-GRECO Cardio-oncology Program, F75013 Paris, France.

Lea K Davis (LK)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Jill H Simmons (JH)

Division of Pediatric Endocrinology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Dan M Roden (DM)

Department of Biomedical Informatics & Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37212, USA.

M Benjamin Shoemaker (MB)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Jane F Ferguson (JF)

Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Jonathan D Mosley (JD)

Department of Biomedical Informatics & Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

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Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Troubles du rythme cardiaque › Fibrillation auriculaire › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Hémodynamique › Pression sanguine › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Mensurations corporelles › Taille › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Facteurs de risque de maladie cardiaque › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic endocrinien › Tests de la fonction thyroïdienne › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Système endocrine › Glandes endocrines › Glande thyroide › Genetic Thyrotropin Regulation of Atrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones hypophysaires › Hormones antéhypophysaires › Thyréostimuline › Genetic Thyrotropin Regulation of Atrial...