Brain functional connectivity mirrors genetic pleiotropy in psychiatric conditions.
autism spectrum disorder
copy-number variant
functional connectivity
pleiotropy
psychiatry
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
19 04 2023
19 04 2023
Historique:
received:
14
04
2022
revised:
13
07
2022
accepted:
11
08
2022
medline:
21
4
2023
pubmed:
5
9
2022
entrez:
4
9
2022
Statut:
ppublish
Résumé
Pleiotropy occurs when a genetic variant influences more than one trait. This is a key property of the genomic architecture of psychiatric disorders and has been observed for rare and common genomic variants. It is reasonable to hypothesize that the microscale genetic overlap (pleiotropy) across psychiatric conditions and cognitive traits may lead to similar overlaps at the macroscale brain level such as large-scale brain functional networks. We took advantage of brain connectivity, measured by resting-state functional MRI to measure the effects of pleiotropy on large-scale brain networks, a putative step from genes to behaviour. We processed nine resting-state functional MRI datasets including 32 726 individuals and computed connectome-wide profiles of seven neuropsychiatric copy-number-variants, five polygenic scores, neuroticism and fluid intelligence as well as four idiopathic psychiatric conditions. Nine out of 19 pairs of conditions and traits showed significant functional connectivity correlations (rFunctional connectivity), which could be explained by previously published levels of genomic (rGenetic) and transcriptomic (rTranscriptomic) correlations with moderate to high concordance: rGenetic-rFunctional connectivity = 0.71 [0.40-0.87] and rTranscriptomic-rFunctional connectivity = 0.83 [0.52; 0.94]. Extending this analysis to functional connectivity profiles associated with rare and common genetic risk showed that 30 out of 136 pairs of connectivity profiles were correlated above chance. These similarities between genetic risks and psychiatric disorders at the connectivity level were mainly driven by the overconnectivity of the thalamus and the somatomotor networks. Our findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, opening avenues to delineate general mechanisms-amenable to intervention-across psychiatric conditions and genetic risks.
Identifiants
pubmed: 36059063
pii: 6691797
doi: 10.1093/brain/awac315
pmc: PMC10319760
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1686-1696Subventions
Organisme : NIMH NIH HHS
ID : RL1 MH083268
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB015922
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119736
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119738
Pays : United States
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Organisme : NINDS NIH HHS
ID : PL1 NS062410
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH100900
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119690
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119739
Pays : United States
Organisme : NIDA NIH HHS
ID : RL1 DA024853
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH111671
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116147
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : U01 AG068057
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH116473
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085953
Pays : United States
Organisme : NLM NIH HHS
ID : RL1 LM009833
Pays : United States
Organisme : NIMH NIH HHS
ID : RL1 MH083270
Pays : United States
Organisme : NIMH NIH HHS
ID : PL1 MH083271
Pays : United States
Organisme : NIDCR NIH HHS
ID : UL1 DE019580
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : RL1 MH083269
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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