PLoS ONE (Jan 2020)

Genome wide association study of incomplete hippocampal inversion in adolescents.

  • Claire Cury,
  • Marzia Antonella Scelsi,
  • 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,
  • IMAGEN Consortium

DOI
https://doi.org/10.1371/journal.pone.0227355
Journal volume & issue
Vol. 15, no. 1
p. e0227355

Abstract

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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.