Genome wide association study of incomplete hippocampal inversion in adolescents

• DOI: 10.1371/journal.pone.0227355
• Publication Date: 2020-01-28T16:33:30Z
• Authors: Claire Cury; Marzia Antonella ...; Roberto Toro; Vincent Frouin; Eric Artiges; Antoine Grigis; Andreas Heinz; Hervé Lemaître; Jean-Luc Martinot; Jean-Baptiste Poline; Michael N. Smolka; Henrik Walter; Gunter Schumann; Andre Altmann; Olivier Colliot
• Keywords: Male; 0301 basic medicine; Adolescent; [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging; Science; 610; Hippocampus; Polymorphism, Single Nucleotide; 03 medical and health sciences; GWAS; Humans; Genetic Predisposition to Disease; Aquaporin 4; Brain Diseases; [SCCO.NEUR]Cognitive science/Neuroscience; Q; R; 600; Neuro-imaging; Temporal Lobe; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; Medicine; Female; Co-Repressor Proteins; Research Article; Genome-Wide Association Study

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.