Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
13
04
2018
accepted:
06
09
2018
revised:
09
08
2018
pubmed:
4
10
2018
medline:
16
3
2021
entrez:
4
10
2018
Statut:
ppublish
Résumé
The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10
Identifiants
pubmed: 30279459
doi: 10.1038/s41380-018-0262-7
pii: 10.1038/s41380-018-0262-7
pmc: PMC6445783
mid: NIHMS1506075
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3053-3065Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIMH NIH HHS
ID : RC2 MH089983
Pays : United States
Organisme : NIDA NIH HHS
ID : RC2 DA029475
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG024904
Pays : United States
Organisme : NIMH NIH HHS
ID : RC2 MH089924
Pays : United States
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