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The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure

Chern-Yee Tan, G; Chu, C; Teng, LY; King Clarence, TC; Ashburner, J; Wood, NW; Frackowiak, RS; (2020) The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure. Neuroimage , Article 117087. 10.1016/j.neuroimage.2020.117087. (In press). Green open access

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Abstract

The androgen receptor (AR), oestrogen receptor alpha (ESR1) and oestrogen receptor beta (ESR2) play essential roles in mediating the effect of sex hormones on sex differences in the brain. Using Voxel-based morphometry (VBM) and gene sizing in two independent samples (discovery n = 173, replication = 61), we determine the common and unique influences on brain sex differences in grey (GM) and white matter (WM) volume between repeat lengths (n) of microsatellite polymorphisms AR(CAG)n, ESR1(TA)n and ESR2(CA)n. In the hypothalamus, temporal lobes, anterior cingulate cortex, posterior insula and prefrontal cortex, we find increased GM volume with increasing AR(CAG)n across sexes, decreasing ESR1(TA)n across sexes and decreasing ESR2(CA)n in females. Uniquely, AR(CAG)n was positively associated with dorsolateral prefrontal and orbitofrontal GM volume and the anterior corona radiata, left superior fronto-occipital fasciculus, thalamus and internal capsule WM volume. ESR1(TA)n was negatively associated with the left superior corona radiata, left cingulum and left inferior longitudinal fasciculus WM volume uniquely. ESR2(CA)n was negatively associated with right fusiform and posterior cingulate cortex uniquely. We thus describe the neuroanatomical correlates of three microsatellite polymorphisms of steroid hormone receptors and their relationship to sex differences.

Type: Article
Title: The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroimage.2020.117087
Publisher version: https://doi.org/10.1016/j.neuroimage.2020.117087
Language: English
Additional information: © 2020 Published by Elsevier Inc. under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10103770
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