Tom Chambers1,2, Richard Anney1, Peter N Taylor3, Alexander Teumer4, Robin P Peeters5, Marco Medici5,6,7, Xavier Caseras1, D Aled Rees8. 1. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. 2. Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, UK. 3. Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK. 4. Institute for Community Medicine, University Medicine Greifswald, Germany. 5. Department of Internal Medicine and Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands. 6. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. 7. Department of Internal Medicine, Radboud University Medical Center, HB Nijmegen, The Netherlands. 8. Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff, UK.
Abstract
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 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 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 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.
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 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 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 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.
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