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 |
| Number of pages | 14 |
| Journal | Nature Neuroscience |
| Volume | 19 |
| Issue number | 12 |
| DOIs | |
| State | Published - 1 Dec 2016 |
| Externally published | Yes |
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In: Nature Neuroscience, Vol. 19, No. 12, 01.12.2016, p. 1569-1582.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Novel genetic loci underlying human intracranial volume identified through genome-wide association
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AU - Heslenfeld, Dirk J.
AU - Ho, Beng Choon
AU - Hoekstra, Pieter J.
AU - Hoffmann, Wolfgang
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AU - Holsboer, Florian
AU - Homuth, Georg
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AU - Ikeda, Masashi
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AU - Pike, G. Bruce
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AU - Reppermund, Simone
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AU - Saykin, Andrew J.
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AU - Sigurdsson, Sigurdur
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AU - Sisodiya, Sanjay M.
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AU - Smoller, Jordan W.
AU - Soininen, Hilkka
AU - Srikanth, Velandai
AU - Steen, Vidar M.
AU - Stott, David J.
AU - Sussmann, Jessika E.
AU - Thalamuthu, Anbupalam
AU - Tiemeier, Henning
AU - Toga, Arthur W.
AU - Traynor, Bryan J.
AU - Troncoso, Juan
AU - Turner, Jessica A.
AU - Tzourio, Christophe
AU - Uitterlinden, Andre G.
AU - Hernández, Maria C.Valdés
AU - Van Der Brug, Marcel
AU - Van Der Lugt, Aad
AU - Van Der Wee, Nic J.A.
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N1 - Publisher Copyright: © 2016 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
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.
UR - http://www.scopus.com/inward/record.url?scp=84989867010&partnerID=8YFLogxK
U2 - 10.1038/nn.4398
DO - 10.1038/nn.4398
M3 - Article
C2 - 27694991
AN - SCOPUS:84989867010
SN - 1097-6256
VL - 19
SP - 1569
EP - 1582
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 12
ER -