TY - JOUR
T1 - Gene Expression has Distinct Associations with Brain Structure and Function in Major Depressive Disorder
AU - Liu, Shu
AU - Abdellaoui, Abdel
AU - Verweij, Karin J. H.
AU - van Wingen, Guido A.
N1 - Funding Information: A.A., K.J.H.V., and G.A.W. contributed equally to this work. This research has been conducted using the REST‐meta‐MDD Project from the DIRECT Consortium and the UK Biobank Resource under Application Number 30091. A.A. and K.J.H.V. are supported by the Foundation Volksbond Rotterdam. This work was supported by a CSC grant to S.L. G.v.W. has received research funding by Philips for an unrelated project. Publisher Copyright: © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2023/3/3
Y1 - 2023/3/3
N2 - Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well as brain anatomy and function are influenced by genetic factors, but the role of gene expression remains unclear. Here, this work investigates how cortical gene expression contributes to structural and functional brain abnormalities in MDD. This work compares the gray matter volume and resting-state functional measures in a Chinese sample of 848 MDD patients and 749 healthy controls, and these case-control differences are then associated with cortical variation of gene expression. While whole gene expression is positively associated with structural abnormalities, it is negatively associated with functional abnormalities. This work observes the relationships of expression levels with brain abnormalities for individual genes, and found that transcriptional correlates of brain structure and function show opposite relations with gene dysregulation in postmortem cortical tissue from MDD patients. This work further identifies genes that are positively or negatively related to structural abnormalities as well as functional abnormalities. The MDD-related genes are enriched for brain tissue, cortical cells, and biological pathways. These findings suggest that distinct genetic mechanisms underlie structural and functional brain abnormalities in MDD, and highlight the importance of cortical gene expression for the development of cortical abnormalities.
AB - Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well as brain anatomy and function are influenced by genetic factors, but the role of gene expression remains unclear. Here, this work investigates how cortical gene expression contributes to structural and functional brain abnormalities in MDD. This work compares the gray matter volume and resting-state functional measures in a Chinese sample of 848 MDD patients and 749 healthy controls, and these case-control differences are then associated with cortical variation of gene expression. While whole gene expression is positively associated with structural abnormalities, it is negatively associated with functional abnormalities. This work observes the relationships of expression levels with brain abnormalities for individual genes, and found that transcriptional correlates of brain structure and function show opposite relations with gene dysregulation in postmortem cortical tissue from MDD patients. This work further identifies genes that are positively or negatively related to structural abnormalities as well as functional abnormalities. The MDD-related genes are enriched for brain tissue, cortical cells, and biological pathways. These findings suggest that distinct genetic mechanisms underlie structural and functional brain abnormalities in MDD, and highlight the importance of cortical gene expression for the development of cortical abnormalities.
KW - brain function
KW - brain structure
KW - gene expression
KW - major depressive disorder
UR - http://www.scopus.com/inward/record.url?scp=85146326811&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/advs.202205486
DO - https://doi.org/10.1002/advs.202205486
M3 - Article
C2 - 36638259
SN - 2198-3844
VL - 10
JO - Advanced Science
JF - Advanced Science
IS - 7
M1 - 2205486
ER -