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Novel genetic loci associated with hippocampal volume

MPG-Autoren
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Guadalupe,  Tulio
Language and Genetics Group, MPI for Psycholinguistics, Max Planck Society;

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Fisher,  Simon E.
Donders Institute for Brain, Cognition and Behaviour, External Organizations;
Language and Genetics Group, MPI for Psycholinguistics, Max Planck Society;

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Francks,  Clyde
Donders Institute for Brain, Cognition and Behaviour, External Organizations;
Language and Genetics Group, MPI for Psycholinguistics, Max Planck Society;

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Volltexte (frei zugänglich)

ncomms13624.pdf
(Verlagsversion), 2MB

Ergänzendes Material (frei zugänglich)

ncomms13624-s1.pdf
(Ergänzendes Material), 3MB

ncomms13624-s2.xlsx
(Ergänzendes Material), 67KB

Zitation

Hibar, D. P., Adams, H. H. H., Jahanshad, N., Chauhan, G., Stein, J. L., Hofer, E., et al. (2017). Novel genetic loci associated with hippocampal volume. Nature Communications, 8: 13624. doi:10.1038/ncomms13624.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002B-A1BC-7
Zusammenfassung
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.