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 & 8 others G. Schumann, D. van t Ent, M. Fornage, B. Franke, S. Debette, S.E. Medland, M. Arfan Ikram, P.M. Thompson

Research output: Contribution to JournalArticleAcademicpeer-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.
LanguageEnglish
Pages1569-1582
JournalNature Neuroscience
Volume19
Issue number12
DOIs
Publication statusPublished - 2016

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Genetic Loci
Genome
Genome-Wide Association Study
Phosphatidylinositol 3-Kinases
Cognition
Genes
Parkinson Disease
Meta-Analysis
Head
Brain
Growth
Genetic Background

Cite this

Adams, H. H. H., Hibar, D. P., Chouraki, V., Stein, J. L., Nyquist, P. A., Renteria, M. E., ... 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
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. ; Launer, L.J. ; Schumann, G. ; van t Ent, D. ; Fornage, M. ; Franke, B. ; Debette, S. ; Medland, S.E. ; Arfan Ikram, M. ; Thompson, P.M. / Novel genetic loci underlying human intracranial volume identified through genome-wide association. In: Nature Neuroscience. 2016 ; Vol. 19, No. 12. pp. 1569-1582.
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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",
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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

Novel genetic loci underlying human intracranial volume identified through genome-wide association. / 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.; Launer, L.J.; Schumann, G.; van t Ent, D.; Fornage, M.; Franke, B.; Debette, S.; Medland, S.E.; Arfan Ikram, M.; Thompson, P.M.

In: Nature Neuroscience, Vol. 19, No. 12, 2016, p. 1569-1582.

Research output: Contribution to JournalArticleAcademicpeer-review

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

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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.

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DO - 10.1038/nn.4398

M3 - Article

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SP - 1569

EP - 1582

JO - Nature Neuroscience

T2 - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

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Adams HHH, Hibar DP, Chouraki V, Stein JL, Nyquist PA, Renteria ME et al. Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience. 2016;19(12):1569-1582. https://doi.org/10.1038/nn.4398