Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/ncomms13624

Type

Journal article

Journal

Nat Commun

Publication Date

18/01/2017

Volume

8

Keywords

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