Novel genetic loci associated with hippocampal volume.

TitleNovel genetic loci associated with hippocampal volume.
Publication TypeJournal Article
Year of Publication2017
AuthorsHibar DP, Adams HHH, Jahanshad N, Chauhan G, Stein JL, Hofer E, Renteria ME, Bis JC, Arias-Vasquez A, M Ikram K et al.
JournalNat Commun
Date Published2017 Jan 18

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.

Alternate JournalNat Commun
PubMed ID28098162
PubMed Central IDPMC5253632
Grant ListT32 MH073526 / MH / NIMH NIH HHS / United States
104036 / / Wellcome Trust / United Kingdom
UL1 TR001863 / TR / NCATS NIH HHS / United States
T32 NS048004 / NS / NINDS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
U54 EB020403 / EB / NIBIB NIH HHS / United States
R00 MH102357 / MH / NIMH NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
K01 MH099232 / MH / NIMH NIH HHS / United States
MC_UU_12013/2 / / Medical Research Council / United Kingdom