Genome wide association study of incomplete hippocampal inversion in adolescents

Claire Cury (1) , Marzia Antonella Scelsi (1) , Roberto Toro (2) , Vincent Frouin (3) , Eric Artiges (4) , Andreas Heinz (5) , Herve Lemaitre (4) , Jean-Luc Martinot (4, 6) , Jean-Baptiste Poline (7, 8) , Michael N Smolka (9) , Henrik Walter (5) , Gunter Schumann (10) , Andre Altmann (1) , Olivier Colliot (11, 12)

1 CMIC - Centre for Medical Image Computing
2 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
3 NEUROSPIN - Service NEUROSPIN
4 U1000 - Neuroimagerie en psychiatrie
5 Department of Psychiatry and Psychotherapy [Berlin]
6 Maison de Solenn [CHU Cochin]
7 McGill University = Université McGill [Montréal, Canada]
8 BIC - McConnell Brain Imaging Center
9 TU Dresden - Technische Universität Dresden = Dresden University of Technology
10 King‘s College London
11 ARAMIS - Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris]
12 ICM - Institut du Cerveau = Paris Brain Institute

Incomplete hippocampal inversion (IHI), also called hippocampal malrotation,is an atypical presentation of the hippocampuspresent 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 cohortobtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5were followed up in a validation cohort comprising 161subjects from the PING study.Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits.Alocus 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 locusimplicatedgenes AQP4and KCTD1. However, neitherthis 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 reachednominal P<=0.013.

Mots clés: Neuro-imaging; Hippocampus; GWAS

Domaines: Imagerie; Neurosciences; Génétique humaine

Claire Cury, Marzia Antonella Scelsi, Roberto Toro, Vincent Frouin, Eric Artiges, et al.. Genome wide association study of incomplete hippocampal inversion in adolescents. PLoS ONE, 2020, 15 (1), ⟨10.1371/journal.pone.0227355⟩. ⟨hal-02416654v2⟩