Genome wide association study of incomplete hippocampal inversion in adolescents.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
05
2019
accepted:
17
12
2019
entrez:
29
1
2020
pubmed:
29
1
2020
medline:
9
4
2020
Statut:
epublish
Résumé
Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate the genetic underpinnings that may contribute to the incomplete inversion during brain development. A total of 1381 subjects contributed to the discovery cohort obtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5 were followed up in a validation cohort comprising 161 subjects from the PING study. Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits. A locus on 18q11.2 (rs9952569; OR = 1.999; Z = 5.502; P = 3.755e-8) showed a significant association with the presence of IHI. A functional annotation of the locus implicated genes AQP4 and KCTD1. However, neither this locus nor the other 16 suggestive loci reached a significant p-value in the validation cohort. The h2 estimate was 0.54 (sd: 0.30) and was significant (Z = 1.8; P = 0.036). The top three genetic correlations of IHI were with traits representing either intelligence or education attainment and reached nominal P< = 0.013.
Identifiants
pubmed: 31990937
doi: 10.1371/journal.pone.0227355
pii: PONE-D-19-12501
pmc: PMC6986744
doi:
Substances chimiques
AQP4 protein, human
0
Aquaporin 4
0
Co-Repressor Proteins
0
KCTD1 protein, human
0
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
e0227355Subventions
Organisme : Medical Research Council
ID : MR/L016311/1
Pays : United Kingdom
Organisme : NIDA NIH HHS
ID : RC2 DA029475
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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