Genome wide association study of incomplete hippocampal inversion in adolescents

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Claire Cury - , University College London, Institut de Recherche en Informatique et Systemes Aleatoires (Author)
  • Marzia Antonella Scelsi - , University College London (Author)
  • Roberto Toro - , French National Centre for Scientific Research (CNRS), Institut Pasteur Paris (Author)
  • Vincent Frouin - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Eric Artiges - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • Antoine Grigis - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Andreas Heinz - , Charité – Universitätsmedizin Berlin (Author)
  • Hervé Lemaitre - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • Jean Luc Martinot - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • Jean Baptiste Poline - , McGill University Health Centre (Author)
  • Michael N. Smolka - , Department of Psychiatry and Psychotherapy, Neuroimaging Center (Author)
  • Henrik Walter - , Charité – Universitätsmedizin Berlin (Author)
  • Gunter Schumann - , King's College London (KCL) (Author)
  • Andre Altmann - , University College London (Author)
  • Olivier Colliot - , Paris Brain Institute, INSERM - Institut national de la santé et de la recherche médicale, French National Centre for Scientific Research (CNRS), Sorbonne Université, INRIA - Institut national de recherche en informatique et en automatique (Author)

Abstract

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.

Details

Original languageEnglish
Article numbere0227355
JournalPloS one
Volume15
Issue number1
Publication statusPublished - 1 Jan 2020
Peer-reviewedYes

External IDs

PubMed 31990937
ORCID /0000-0001-5398-5569/work/161890722

Keywords

ASJC Scopus subject areas