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Novel genetic loci associated with hippocampal volume
Journal article   Open access   Peer reviewed

Novel genetic loci associated with hippocampal volume

Derrek P Hibar, Hieab H. H Adams, Neda Jahanshad, Ganesh Chauhan, Jason L Stein, Edith Hofer, Miguel E Renteria, Joshua C Bis, Alejano Arias-Vasquez, M. Kamran Ikram, …
Nature communications, Vol.8, 13624
01/18/2017
DOI: 10.1038/ncomms13624
PMCID: PMC5253632
PMID: 28098162
url
https://doi.org/10.1038/ncomms13624View
Published (Version of record) Open Access

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(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
ALZHEIMERS-DISEASE BIPOLAR DISORDER BRAIN-REGIONS COMMON VARIANTS GENOME-WIDE ASSOCIATION MEMORY METAANALYSIS SUBFIELDS SUSCEPTIBILITY LOCI TEMPORAL-LOBE EPILEPSY

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