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Genome wide association study of incomplete hippocampal inversion in adolescents

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Claire Cury, Marzia Antonella Scelsi, Roberto Toro, Vincent Frouin, Eric Artiges, Antoine Grigis, Andreas Heinz, Hervé Lemaitre, Jean Luc Martinot, Jean Baptiste Poline, Michael N. Smolka, Henrik Walter, Gunter Schumann, Andre Altmann, Olivier Colliot

Original languageEnglish
Article numbere0227355
JournalPLoS ONE
Issue number1
Publication statusPublished - 1 Jan 2020

King's Authors


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.

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