Novel genetic loci associated with hippocampal volume

Nat Commun. 2017 Jan 18;8:13624. doi: 10.1038/ncomms13624.

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Child
  • Cohort Studies
  • Dipeptidyl Peptidase 4 / genetics
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glycoproteins / genetics
  • Hippocampus / growth & development*
  • Humans
  • Male
  • Methionine Sulfoxide Reductases / genetics
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Organ Size
  • Protein-Serine-Threonine Kinases / genetics
  • Young Adult

Substances

  • ASTN2 protein, human
  • Glycoproteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Methionine Sulfoxide Reductases
  • MSRB3 protein, human
  • MAST4 protein, human
  • Protein-Serine-Threonine Kinases
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4

Grant support