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Novel genetic loci associated with hippocampal volume

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

Authors/Editors: Hibar DP, Hieab H.H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, Edith Hofer, Miguel E. Renteria, Joshua C. Bis et al. (i.a. Müller-Myhsok B).
Publication Date: 2017

2017_01_hibar


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 (rg¼ _0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for
neuropsychiatric illness.

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