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Effects of thyroid status on regional brain volumes: a diagnostic and genetic imaging study in UK Biobank

Chambers, Tom, Anney, Richard ORCID:, Taylor, Peter N. ORCID:, Teumer, Alexander, Peeters, Robin P., Medici, Marco, Caseras, Xavier ORCID: and Rees, D. Aled ORCID: 2021. Effects of thyroid status on regional brain volumes: a diagnostic and genetic imaging study in UK Biobank. Journal of Clinical Endocrinology and Metabolism 106 (3) , pp. 688-696. 10.1210/clinem/dgaa903

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Background Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit hyperactivity disorder (ADHD). However, the brain structures involved are unknown and it is unclear if the adult brain is also susceptible to changes in thyroid status. Methods We used international classification of disease-10 codes, polygenic thyroid scores at different thresholds of association with thyroid traits (pT-values) and image-derived phenotypes in UK Biobank (n=18,825) to investigate the effects of a recorded diagnosis of thyroid disease and genetic risk for thyroid status on cerebellar and subcortical grey matter volume. Regional genetic pleiotropy between thyroid status and ADHD was explored using the GWAS-pairwise method. Results A recorded diagnosis of hypothyroidism (n=419) was associated with significant reductions in total cerebellar and pallidum grey matter volumes (β[95%CI] = -0.14[-0.23, -0.06], p = 0.0005 and β[95%CI] = -0.12[-0.20, -0.04], p = 0.0042, respectively), mediated in part by increases in Body Mass Index. Whilst we found no evidence for total cerebellar volume alterations with increased polygenic scores for any thyroid trait, opposing influences of increased polygenic scores for hypo- and hyperthyroidism were found in the pallidum (pT<1e-3: β[95%CI] = -0.02[-0.03,-0.01], p = 0.0003 and pT<1e-7: β[95%CI] = 0.02[0.01,0.03], p = 0.0003, respectively). Neither hypo- nor hyperthyroidism showed evidence of regional genetic pleiotropy with ADHD. Conclusions Thyroid status affects grey matter volume in adults, particularly at the level of the cerebellum and pallidum, with potential implications for the regulation of motor, cognitive and affective function.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Cardiff University Brain Research Imaging Centre (CUBRIC)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Oxford University Press
ISSN: 0021-972X
Funders: Wellcome Trust
Date of First Compliant Deposit: 7 December 2020
Date of Acceptance: 26 November 2020
Last Modified: 09 May 2023 23:59

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