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; Alejandro Arias-Vasquez; M. Kamran Ikram; Sylvane Desrivieres; Meike W. Vernooij; Lucija Abramovic; Saud Alhusaini; Najaf Amin; Micael Andersson; Konstantinos Arfanakis; Benjamin S. Aribisala; Nicola J. Armstrong; Lavinia Athanasiu; Tomas Axelsson; Ashley H. Beecham; Alexa Beiser; Manon Bernard; Susan H. Blanton; Marc M. Bohlken; Marco P. Boks; Janita Bralten; Adam M. Brickman; Owen Carmichael; M. Mallar Chakravarty; Qiang Chen; Christopher R. K. Ching; Vincent Chouraki; Gabriel Cuellar-Partida; Fabrice Crivello; Anouk Den Braber; Nhat Trung Doan; Stefan Ehrlich; Sudheer Giddaluru; Aaron L. Goldman; Rebecca F. Gottesman; Oliver Grimm; Michael E. Griswold; Tulio Guadalupe; Boris A. Gutman; Johanna Hass; Unn K. Haukvik; David Hoehn; Han G. Brunner; Author collaboration

doi:10.1038/ncomms13624

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, Alejandro Arias-Vasquez, M. Kamran Ikram^*, Sylvane Desrivieres, Meike W. Vernooij, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia AthanasiuTomas Axelsson, Ashley H. Beecham, Alexa Beiser, Manon Bernard, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Vincent Chouraki, Gabriel Cuellar-Partida, Fabrice Crivello, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Boris A. Gutman, Johanna Hass, Unn K. Haukvik, David Hoehn, Han G. Brunner, Author collaboration

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	13624
Number of pages	12
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms13624
Publication status	Published - 18 Jan 2017
Externally published	Yes

Keywords

Genome-wide association
Temporal-lobe epilepsy
Susceptibility loci
Alzheimers-disease
Bipolar disorder
Common variants
Brain-regions
Memory
Subfields
Metaanalysis

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Hibar, D. P., Adams, H. H. H., Jahanshad, N., Chauhan, G., Stein, J. L., Hofer, E., Renteria, M. E., Bis, J. C., Arias-Vasquez, A., Ikram, M. K., Desrivieres, S., Vernooij, M. W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B. S., Armstrong, N. J., ... Author collaboration (2017). Novel genetic loci associated with hippocampal volume. Nature Communications, 8, Article 13624. https://doi.org/10.1038/ncomms13624

@article{a28bd47c77184bed9add789f4ec66f5e,

title = "Novel genetic loci associated with hippocampal volume",

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.",

keywords = "Genome-wide association, Temporal-lobe epilepsy, Susceptibility loci, Alzheimers-disease, Bipolar disorder, Common variants, Brain-regions, Memory, Subfields, Metaanalysis",

author = "Hibar, {Derrek P.} and Adams, {Hieab H. H.} and Neda Jahanshad and Ganesh Chauhan and Stein, {Jason L.} and Edith Hofer and Renteria, {Miguel E.} and Bis, {Joshua C.} and Alejandro Arias-Vasquez and Ikram, {M. Kamran} and Sylvane Desrivieres and Vernooij, {Meike W.} and Lucija Abramovic and Saud Alhusaini and Najaf Amin and Micael Andersson and Konstantinos Arfanakis and Aribisala, {Benjamin S.} and Armstrong, {Nicola J.} and Lavinia Athanasiu and Tomas Axelsson and Beecham, {Ashley H.} and Alexa Beiser and Manon Bernard and Blanton, {Susan H.} and Bohlken, {Marc M.} and Boks, {Marco P.} and Janita Bralten and Brickman, {Adam M.} and Owen Carmichael and Chakravarty, {M. Mallar} and Qiang Chen and Ching, {Christopher R. K.} and Vincent Chouraki and Gabriel Cuellar-Partida and Fabrice Crivello and {Den Braber}, Anouk and Doan, {Nhat Trung} and Stefan Ehrlich and Sudheer Giddaluru and Goldman, {Aaron L.} and Gottesman, {Rebecca F.} and Oliver Grimm and Griswold, {Michael E.} and Tulio Guadalupe and Gutman, {Boris A.} and Johanna Hass and Haukvik, {Unn K.} and David Hoehn and Brunner, {Han G.} and {Author collaboration}",

year = "2017",

month = jan,

day = "18",

doi = "10.1038/ncomms13624",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Doan, NT, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Brunner, HG & Author collaboration 2017, 'Novel genetic loci associated with hippocampal volume', Nature Communications, vol. 8, 13624. https://doi.org/10.1038/ncomms13624

TY - JOUR

T1 - Novel genetic loci associated with hippocampal volume

AU - Hibar, Derrek P.

AU - Adams, Hieab H. H.

AU - Jahanshad, Neda

AU - Chauhan, Ganesh

AU - Stein, Jason L.

AU - Hofer, Edith

AU - Renteria, Miguel E.

AU - Bis, Joshua C.

AU - Arias-Vasquez, Alejandro

AU - Ikram, M. Kamran

AU - Desrivieres, Sylvane

AU - Vernooij, Meike W.

AU - Abramovic, Lucija

AU - Alhusaini, Saud

AU - Amin, Najaf

AU - Andersson, Micael

AU - Arfanakis, Konstantinos

AU - Aribisala, Benjamin S.

AU - Armstrong, Nicola J.

AU - Athanasiu, Lavinia

AU - Axelsson, Tomas

AU - Beecham, Ashley H.

AU - Beiser, Alexa

AU - Bernard, Manon

AU - Blanton, Susan H.

AU - Bohlken, Marc M.

AU - Boks, Marco P.

AU - Bralten, Janita

AU - Brickman, Adam M.

AU - Carmichael, Owen

AU - Chakravarty, M. Mallar

AU - Chen, Qiang

AU - Ching, Christopher R. K.

AU - Chouraki, Vincent

AU - Cuellar-Partida, Gabriel

AU - Crivello, Fabrice

AU - Den Braber, Anouk

AU - Doan, Nhat Trung

AU - Ehrlich, Stefan

AU - Giddaluru, Sudheer

AU - Goldman, Aaron L.

AU - Gottesman, Rebecca F.

AU - Grimm, Oliver

AU - Griswold, Michael E.

AU - Guadalupe, Tulio

AU - Gutman, Boris A.

AU - Hass, Johanna

AU - Haukvik, Unn K.

AU - Hoehn, David

AU - Brunner, Han G.

AU - Author collaboration

PY - 2017/1/18

Y1 - 2017/1/18

N2 - 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.

AB - 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.

KW - Genome-wide association

KW - Temporal-lobe epilepsy

KW - Susceptibility loci

KW - Alzheimers-disease

KW - Bipolar disorder

KW - Common variants

KW - Brain-regions

KW - Memory

KW - Subfields

KW - Metaanalysis

U2 - 10.1038/ncomms13624

DO - 10.1038/ncomms13624

M3 - Article

C2 - 28098162

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 13624

ER -

Novel genetic loci associated with hippocampal volume

Abstract

Keywords

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