Open AccessGenome wide association study of incomplete hippocampal inversion in adolescents
Author(s) -
Claire Cury,
Marzia Antonella Scelsi,
Roberto Toro,
Vincent Frouin,
Éric Artiges,
Antoine Grigis,
Andreas Heinz,
Hervé Lemaître,
JeanLuc Martinot,
JeanBaptiste Poline,
Michael N. Smolka,
Henrik Walter,
Günter Schumann,
André Altmann,
Olivier Colliot
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0227355
Subject(s) - genome wide association study , cohort , locus (genetics) , heritability , genetic association , genetics , missing heritability problem , 1000 genomes project , biology , medicine , single nucleotide polymorphism , gene , genotype
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 h 2 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.