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Nature Research, Nature Communications, 1(8), 2017

DOI: 10.1038/ncomms13624

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Novel genetic loci associated with hippocampal volume

Journal article published in 2017 by Nj van der Wee, Dennis van't Ent, Jl L. Stein, Hieab H. Hh Adams, Neda Jahanshad, Ganesh Chauhan, Me E. (Miguel) Renteria, Mw W. (Meike) Vernooij, Edith Hofer, Kn N. (Kjetil N.) Jørgensen, Kjetil N. Jorgensen, M. Kamran Ikram, Alejandro Arias-Vasquez, M. Kamran Ikram, Sylvane Desrivières and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractThe 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.