Chromosomal inversion polymorphisms shape human brain morphology.
CP: Genomics
CP: Neuroscience
brain morphology
gene regulation
inversion polymorphism
magnetic resonance imaging
molecular QTL
neurodevelopment
segmental duplication
structural variant
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
29 08 2023
29 08 2023
Historique:
received:
23
12
2022
revised:
27
06
2023
accepted:
13
07
2023
medline:
4
9
2023
pubmed:
28
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
The impact of chromosomal inversions on human brain morphology remains underexplored. We studied 35 common inversions classified from genotypes of 33,018 adults with European ancestry. The inversions at 2p22.3, 16p11.2, and 17q21.31 reach genome-wide significance, followed by 8p23.1 and 6p21.33, in their association with cortical and subcortical morphology. The 17q21.31, 8p23.1, and 16p11.2 regions comprise the LRRC37, OR7E, and NPIP duplicated gene families. We find the 17q21.31 MAPT inversion region, known for harboring neurological risk, to be the most salient locus among common variants for shaping and patterning the cortex. Overall, we observe the inverted orientations decreasing brain size, with the exception that the 2p22.3 inversion is associated with increased subcortical volume and the 8p23.1 inversion is associated with increased motor cortex. These significant inversions are in the genomic hotspots of neuropsychiatric loci. Our findings are generalizable to 3,472 children and demonstrate inversions as essential genetic variation to understand human brain phenotypes.
Identifiants
pubmed: 37505983
pii: S2211-1247(23)00907-5
doi: 10.1016/j.celrep.2023.112896
pmc: PMC10508191
mid: NIHMS1928249
pii:
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
112896Subventions
Organisme : NIMH NIH HHS
ID : R01 MH118281
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG061163
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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