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

H.H.H. Adams; D.P. Hibar; V. Chouraki; J.L. Stein; P.A. Nyquist; M.E. Renteria; S. Trompet; A. Arias Vazquez; S. Seshadri; S. Desrivieres; A. den Braber; D.I. Boomsma; E.J.C. de Geus; I.O. Fedko; J.J. Hottenga; H.E. Hulshoff Pol; B.W.J.H. Penninx; A.J. de Craen; M.J. Wright; L.J. Launer; G. Schumann; D. van t Ent; M. Fornage; B. Franke; S. Debette; S.E. Medland; M. Arfan Ikram; P.M. Thompson

doi:10.1038/nn.4398

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

H.H.H. Adams, D.P. Hibar, V. Chouraki, J.L. Stein, P.A. Nyquist, M.E. Renteria, S. Trompet, A. Arias Vazquez, S. Seshadri, S. Desrivieres, A. den Braber, D.I. Boomsma, E.J.C. de Geus, I.O. Fedko, J.J. Hottenga, H.E. Hulshoff Pol, B.W.J.H. Penninx, A.J. de Craen, M.J. Wright, L.J. LaunerG. Schumann, D. van t Ent, M. Fornage, B. Franke, S. Debette, S.E. Medland, M. Arfan Ikram, P.M. Thompson

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

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 (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.

Original language	English
Pages (from-to)	1569-1582
Journal	Nature Neuroscience
Volume	19
Issue number	12
DOIs	https://doi.org/10.1038/nn.4398
Publication status	Published - 2016

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Adams, H. H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Renteria, M. E., Trompet, S., Arias Vazquez, A., Seshadri, S., Desrivieres, S., den Braber, A., Boomsma, D. I., de Geus, E. J. C., Fedko, I. O., Hottenga, J. J., Hulshoff Pol, H. E., Penninx, B. W. J. H., de Craen, A. J., Wright, M. J., ... Thompson, P. M. (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{e355ae092997486e98e5c8968be7f4c4,

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 (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.",

author = "H.H.H. Adams and D.P. Hibar and V. Chouraki and J.L. Stein and P.A. Nyquist and M.E. Renteria and S. Trompet and {Arias Vazquez}, A. and S. Seshadri and S. Desrivieres and {den Braber}, A. and D.I. Boomsma and {de Geus}, E.J.C. and I.O. Fedko and J.J. Hottenga and {Hulshoff Pol}, H.E. and B.W.J.H. Penninx and {de Craen}, A.J. and M.J. Wright and L.J. Launer and G. Schumann and {van t Ent}, D. and M. Fornage and B. Franke and S. Debette and S.E. Medland and {Arfan Ikram}, M. and P.M. Thompson",

year = "2016",

doi = "10.1038/nn.4398",

language = "English",

volume = "19",

pages = "1569--1582",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "12",

}

Adams, HHH, Hibar, DP, Chouraki, V, Stein, JL, Nyquist, PA, Renteria, ME, Trompet, S, Arias Vazquez, A, Seshadri, S, Desrivieres, S, den Braber, A , Boomsma, DI , de Geus, EJC, Fedko, IO, Hottenga, JJ, Hulshoff Pol, HE, Penninx, BWJH, de Craen, AJ, Wright, MJ, Launer, LJ, Schumann, G, van t Ent, D, Fornage, M, Franke, B, Debette, S, Medland, SE, Arfan Ikram, M & Thompson, PM 2016, 'Novel genetic loci underlying human intracranial volume identified through genome-wide association', Nature Neuroscience, vol. 19, no. 12, pp. 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, H.H.H.

AU - Hibar, D.P.

AU - Chouraki, V.

AU - Stein, J.L.

AU - Nyquist, P.A.

AU - Renteria, M.E.

AU - Trompet, S.

AU - Arias Vazquez, A.

AU - Seshadri, S.

AU - Desrivieres, S.

AU - den Braber, A.

AU - Boomsma, D.I.

AU - de Geus, E.J.C.

AU - Fedko, I.O.

AU - Hottenga, J.J.

AU - Hulshoff Pol, H.E.

AU - Penninx, B.W.J.H.

AU - de Craen, A.J.

AU - Wright, M.J.

AU - Launer, L.J.

AU - Schumann, G.

AU - van t Ent, D.

AU - Fornage, M.

AU - Franke, B.

AU - Debette, S.

AU - Medland, S.E.

AU - Arfan Ikram, M.

AU - Thompson, P.M.

PY - 2016

Y1 - 2016

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 (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 (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.

U2 - 10.1038/nn.4398

DO - 10.1038/nn.4398

M3 - Article

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

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