Novel genetic loci associated with hippocampal volume



Hibar, Derrek P, Adams, Hieab HH, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran
et al (show 322 more authors) (2017) Novel genetic loci associated with hippocampal volume. NATURE COMMUNICATIONS, 8 (1). 13624-.

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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 (r<sub>g</sub>=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Item Type: Article
Uncontrolled Keywords: Hippocampus, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Glycoproteins, Microtubule-Associated Proteins, Nerve Tissue Proteins, Organ Size, Cohort Studies, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Genome-Wide Association Study, Young Adult, Methionine Sulfoxide Reductases, Genetic Loci, Dipeptidyl Peptidase 4, Protein Serine-Threonine Kinases
Depositing User: Symplectic Admin
Date Deposited: 23 Feb 2017 08:18
Last Modified: 19 Jan 2023 07:16
DOI: 10.1038/ncomms13624
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3006001