Phenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences Between Thyroid Disorders

Overview

Journal J Clin Med

Specialty General Medicine

Date 2018 Sep 26

PMID 30248900

Citations 6

Authors

Silvia Ravera

Nancy Carrasco

Joel Gelernter

Renato Polimanti

Affiliations

Soon will be listed here.

Abstract

Background: The thyroid plays a key role in development and homeostasis, but it has been difficult to establish causality with diseases and phenotypic traits because of several potential confounders.

Methods: To determine the causal effect of euthyroid function, we conducted a two-sample Mendelian randomization study of euthyroid thyrotropin (TSH) and free thyroxine (FT4) levels with respect to 2419 traits assessed in 337,199 individuals from UK Biobank. Additionally, we investigated the molecular differences between hypothyroidism and hyperthyroidism using genome-wide data.

Results: After multiple testing correction, sixteen traits appear to be affected by genetically-determined euthyroid TSH, including multiple thyroid-related traits, e.g., hypothyroidism ( = 2.39 × 10), height ( = 2.76 × 10), body fat distribution (impedance of whole body, = 4.43 × 10), pulse rate ( = 2.84 × 10), female infertility ( = 4.91 × 10), and hearing aid use ( = 7.10 × 10). Moreover, we found a consistent genetic correlation between hypothyroidism and hyperthyroidism ( = 0.45, = 5.45 × 10) with several immune pathways shared between these diseases. Two molecular pathways survived multiple testing correction for specificity to hyperthyroidism, JAK/STAT signaling ( = 1.02 × 10) and Rac guanyl-nucleotide exchange factor activity ( = 4.39 × 10).

Conclusion: Our data shed new light on the inter-individual variability of euthyroid function and the molecular mechanisms of the two thyroid disorders investigated.

Citing Articles

Disentangling sex differences in the shared genetic architecture of posttraumatic stress disorder, traumatic experiences, and social support with body size and composition.

Carvalho C, Wendt F, Pathak G, Maihofer A, Stein D, Sumner J Neurobiol Stress. 2021; 15:100400.

PMID: 34611531 PMC: 8477211. DOI: 10.1016/j.ynstr.2021.100400.

Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study.

Bountress K, Wendt F, Bustamante D, Agrawal A, Webb B, Gillespie N Alcohol Clin Exp Res. 2021; 45(8):1616-1623.

PMID: 34120358 PMC: 8429238. DOI: 10.1111/acer.14649.

Multi-environment gene interactions linked to the interplay between polysubstance dependence and suicidality.

Polimanti R, Levey D, Pathak G, Wendt F, Nunez Y, Ursano R Transl Psychiatry. 2021; 11(1):34.

PMID: 33431810 PMC: 7801457. DOI: 10.1038/s41398-020-01153-1.

Dissecting the genetic association of C-reactive protein with PTSD, traumatic events, and social support.

Carvalho C, Wendt F, Maihofer A, Stein D, Stein M, Sumner J Neuropsychopharmacology. 2020; 46(6):1071-1077.

PMID: 32179874 PMC: 8115274. DOI: 10.1038/s41386-020-0655-6.

Association of Economic Status and Educational Attainment With Posttraumatic Stress Disorder: A Mendelian Randomization Study.

Polimanti R, Ratanatharathorn A, Maihofer A, Choi K, Stein M, Morey R JAMA Netw Open. 2019; 2(5):e193447.

PMID: 31050786 PMC: 6503495. DOI: 10.1001/jamanetworkopen.2019.3447.

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