Effects of Thyroid Status on Regional Brain Volumes: A Diagnostic and Genetic Imaging Study in UK Biobank.

Tom Chambers,Peter N Taylor,Robin P Peeters,Alexander Teumer,Marco Medici,Xavier Caseras,D Aled Rees,Richard Anney

doi:10.1210/clinem/dgaa903

Abstract

BackgroundThyroid 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.MethodsWe 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 gray matter volume. Regional genetic pleiotropy between thyroid status and ADHD was explored using the GWAS-pairwise method.ResultsA recorded diagnosis of hypothyroidism (n = 419) was associated with significant reductions in total cerebellar and pallidum gray 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. While 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.ConclusionsThyroid status affects gray 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.

Highlights

Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit/hyperactivity disorder (ADHD)
We found no relationships across any thyroid trait at any P value thresholds (PT)-value reaching our significance threshold when controlling false discovery rate (FDR) < 0.05 (Fig. 2, Supplementary Table 6 [10]), opposing effects in the pallidum of increasing polygenic scores for hyper- and hypothyroidism were close to this threshold
We used a combination of a recorded diagnosis and genetic risk scores to confirm an effect of thyroid status on gray matter volume, notably at the level of the cerebellum and pallidum

Summary

Introduction

Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit/hyperactivity disorder (ADHD). Methods: We used International Classification of Disease-10 codes, polygenic thyroid scores at different thresholds of association with thyroid traits (PT-values), and imagederived 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 gray 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 gray 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. While we found no evidence for total cerebellar volume alterations with increased polygenic scores for any thyroid trait, opposing

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Results

Conclusion