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