Novel genetic loci underlying human intracranial volume identified through genome-wide association

Hieab H. H. Adams; Derrek P. Hibar; Vincent Chouraki; Jason L. Stein; Paul A. Nyquist; Miguel E. Renteria; Stella Trompet; Alejandro Arias-Vasquez; Sudha Seshadri; Sylvane Desrivieres; Ashley H. Beecham; Neda Jahanshad; Katharine Wittfeld; Sven J. Van der Lee; Lucija Abramovic; Saud Alhusaini; Najaf Amin; Micael Andersson; Konstantinos Arfanakis; Benjamin S. Aribisala; Nicola J. Armstrong; Lavinia Athanasiu; Tomas Axelsson; Alexa Beiser; Manon Bernard; Joshua C. Bis; Laura M. E. Blanken; Susan H. Blanton; Marc M. Bohlken; Marco P. Boks; Janita Bralten; Adam M. Brickman; Owen Carmichael; M. Mallar Chakravarty; Ganesh Chauhan; Qiang Chen; Christopher R. K. Ching; Gabriel Cuellar-Partida; Anouk Den Braber; Nhat Trung Doan; Stefan Ehrlich; Jennifer S. Richards; Lianne Schmaal; Albert V. Smith; Dennis Van der Meer; Daan Van Rooij; Catharina A. Hartman; Pieter J. Hoekstra; Brenda W. J. H. Penninx; Marie Jose Van Tol; Wiro J. Niessen; Alzheimer's Dis Neuroimaging Initi; EPIGEN; IMAGEN; SYS

doi:10.1038/nn.4398

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Hieab H. H. Adams, Derrek P. Hibar, Vincent Chouraki, Jason L. Stein, Paul A. Nyquist, Miguel E. Renteria, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivieres, Ashley H. Beecham, Neda Jahanshad, Katharine Wittfeld, Sven J. Van der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. AribisalaNicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Alexa Beiser, Manon Bernard, Joshua C. Bis, Laura M. E. Blanken, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Ganesh Chauhan, Qiang Chen, Christopher R. K. Ching, Gabriel Cuellar-Partida, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Jennifer S. Richards, Lianne Schmaal, Albert V. Smith, Dennis Van der Meer, Daan Van Rooij, Catharina A. Hartman, Pieter J. Hoekstra, Brenda W. J. H. Penninx, Marie Jose Van Tol, Wiro J. Niessen, Alzheimer's Dis Neuroimaging Initi, EPIGEN, IMAGEN, SYS

Onderzoeksoutput › Academic › peer review

172 Citaten (Scopus)

Samenvatting

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Originele taal-2	English
Pagina's (van-tot)	1569-1582
Aantal pagina's	14
Tijdschrift	Nature neuroscience
Volume	19
Nummer van het tijdschrift	12
DOI's	https://doi.org/10.1038/nn.4398
Status	Published - dec.-2016

Toegang tot document

10.1038/nn.4398

Handle.net

Permanente koppeling

Document onder embargo

Novel genetic loci underlying human intracranial volume identified through genome
Final publisher's version, 1,21 MB
Kopie aanvragen

Citeer dit

Adams, H. H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Renteria, M. E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivieres, S., Beecham, A. H., Jahanshad, N., Wittfeld, K., Van der Lee, S. J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., ... SYS (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature neuroscience, 19(12), 1569-1582. https://doi.org/10.1038/nn.4398

@article{f227c90a5d2a41c8a65b5cb41250ef07,

title = "Novel genetic loci underlying human intracranial volume identified through genome-wide association",

abstract = "Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.",

keywords = "COMMON VARIANTS, 17Q21.31 MICRODELETION, PARKINSONS-DISEASE, ALZHEIMERS-DISEASE, HEAD CIRCUMFERENCE, BRAIN SIZE, IGF-I, METAANALYSIS, CONSORTIUM, GROWTH",

author = "Adams, {Hieab H. H.} and Hibar, {Derrek P.} and Vincent Chouraki and Stein, {Jason L.} and Nyquist, {Paul A.} and Renteria, {Miguel E.} and Stella Trompet and Alejandro Arias-Vasquez and Sudha Seshadri and Sylvane Desrivieres and Beecham, {Ashley H.} and Neda Jahanshad and Katharine Wittfeld and {Van der Lee}, {Sven J.} 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 Alexa Beiser and Manon Bernard and Bis, {Joshua C.} and Blanken, {Laura M. E.} 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 Ganesh Chauhan and Qiang Chen and Ching, {Christopher R. K.} and Gabriel Cuellar-Partida and {Den Braber}, Anouk and Doan, {Nhat Trung} and Stefan Ehrlich and Richards, {Jennifer S.} and Lianne Schmaal and Smith, {Albert V.} and {Van der Meer}, Dennis and {Van Rooij}, Daan and Hartman, {Catharina A.} and Hoekstra, {Pieter J.} and Penninx, {Brenda W. J. H.} and {Van Tol}, {Marie Jose} and Niessen, {Wiro J.} and {Alzheimer's Dis Neuroimaging Initi} and EPIGEN and IMAGEN and SYS",

year = "2016",

month = dec,

doi = "10.1038/nn.4398",

language = "English",

volume = "19",

pages = "1569--1582",

journal = "Nature neuroscience",

issn = "1097-6256",

publisher = "NATURE AMERICA INC",

number = "12",

}

Adams, HHH, Hibar, DP, Chouraki, V, Stein, JL, Nyquist, PA, Renteria, ME, Trompet, S, Arias-Vasquez, A, Seshadri, S, Desrivieres, S, Beecham, AH, Jahanshad, N, Wittfeld, K, Van der Lee, SJ, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beiser, A, Bernard, M, Bis, JC, Blanken, LME, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chauhan, G, Chen, Q, Ching, CRK, Cuellar-Partida, G, Den Braber, A, Doan, NT, Ehrlich, S, Richards, JS, Schmaal, L, Smith, AV, Van der Meer, D, Van Rooij, D, Hartman, CA , Hoekstra, PJ, Penninx, BWJH, Van Tol, MJ , Niessen, WJ, Alzheimer's Dis Neuroimaging Initi, EPIGEN, IMAGEN & SYS 2016, 'Novel genetic loci underlying human intracranial volume identified through genome-wide association', Nature neuroscience, vol. 19, nr. 12, blz. 1569-1582. https://doi.org/10.1038/nn.4398

TY - JOUR

T1 - Novel genetic loci underlying human intracranial volume identified through genome-wide association

AU - Adams, Hieab H. H.

AU - Hibar, Derrek P.

AU - Chouraki, Vincent

AU - Stein, Jason L.

AU - Nyquist, Paul A.

AU - Renteria, Miguel E.

AU - Trompet, Stella

AU - Arias-Vasquez, Alejandro

AU - Seshadri, Sudha

AU - Desrivieres, Sylvane

AU - Beecham, Ashley H.

AU - Jahanshad, Neda

AU - Wittfeld, Katharine

AU - Van der Lee, Sven J.

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 - Beiser, Alexa

AU - Bernard, Manon

AU - Bis, Joshua C.

AU - Blanken, Laura M. E.

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 - Chauhan, Ganesh

AU - Chen, Qiang

AU - Ching, Christopher R. K.

AU - Cuellar-Partida, Gabriel

AU - Den Braber, Anouk

AU - Doan, Nhat Trung

AU - Ehrlich, Stefan

AU - Richards, Jennifer S.

AU - Schmaal, Lianne

AU - Smith, Albert V.

AU - Van der Meer, Dennis

AU - Van Rooij, Daan

AU - Hartman, Catharina A.

AU - Hoekstra, Pieter J.

AU - Penninx, Brenda W. J. H.

AU - Van Tol, Marie Jose

AU - Niessen, Wiro J.

AU - Alzheimer's Dis Neuroimaging Initi

AU - EPIGEN

AU - IMAGEN

AU - SYS

PY - 2016/12

Y1 - 2016/12

N2 - Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

AB - Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

KW - COMMON VARIANTS

KW - 17Q21.31 MICRODELETION

KW - PARKINSONS-DISEASE

KW - ALZHEIMERS-DISEASE

KW - HEAD CIRCUMFERENCE

KW - BRAIN SIZE

KW - IGF-I

KW - METAANALYSIS

KW - CONSORTIUM

KW - GROWTH

U2 - 10.1038/nn.4398

DO - 10.1038/nn.4398

M3 - Article

C2 - 27694991

SN - 1097-6256

VL - 19

SP - 1569

EP - 1582

JO - Nature neuroscience

JF - Nature neuroscience

IS - 12

ER -

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Samenvatting

Toegang tot document

Handle.net

Document onder embargo

Vingerafdruk

Citeer dit