Abstract
The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
Original language | English |
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Pages (from-to) | 3945 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 26 Sep 2018 |
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Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. / Vojinovic, Dina; Adams, Hieab H; Jian, Xueqiu; Yang, Qiong; Smith, Albert Vernon; Bis, Joshua C; Teumer, Alexander; Scholz, Markus; Armstrong, Nicola J; Hofer, Edith; Saba, Yasaman; Luciano, Michelle; Bernard, Manon; Trompet, Stella; Yang, Jingyun; Gillespie, Nathan A; van der Lee, Sven J; Neumann, Alexander; Ahmad, Shahzad; Andreassen, Ole A; Ames, David; Amin, Najaf; Arfanakis, Konstantinos; Bastin, Mark E; Becker, Diane M; Beiser, Alexa S; Beyer, Frauke; Brodaty, Henry; Bryan, R Nick; Bülow, Robin; Dale, Anders M; De Jager, Philip L; Deary, Ian J; DeCarli, Charles; Fleischman, Debra A; Gottesman, Rebecca F; van der Grond, Jeroen; Gudnason, Vilmundur; Harris, Tamara B; Homuth, Georg; Knopman, David S; Kwok, John B; Lewis, Cora E; Li, Shuo; Loeffler, Markus; Lopez, Oscar L; Maillard, Pauline; El Marroun, Hanan; Mather, Karen A; Mosley, Thomas H; Muetzel, Ryan L; Nauck, Matthias; Nyquist, Paul A; Panizzon, Matthew S; Pausova, Zdenka; Psaty, Bruce M; Rice, Ken; Rotter, Jerome I; Royle, Natalie; Satizabal, Claudia L; Schmidt, Reinhold; Schofield, Peter R; Schreiner, Pamela J; Sidney, Stephen; Stott, David J; Thalamuthu, Anbupalam; Uitterlinden, Andre G; Valdés Hernández, Maria C; Vernooij, Meike W; Wen, Wei; White, Tonya; Witte, A Veronica; Wittfeld, Katharina; Wright, Margaret J; Yanek, Lisa R; Tiemeier, Henning; Kremen, William S; Bennett, David A; Jukema, J Wouter; Paus, Tomas; Wardlaw, Joanna M; Schmidt, Helena; Sachdev, Perminder S; Villringer, Arno; Grabe, Hans Jörgen; Longstreth, W T; van Duijn, Cornelia M; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Fornage, Myriam.
In: Nature Communications, Vol. 9, No. 1, 26.09.2018, p. 3945.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume
AU - Vojinovic, Dina
AU - Adams, Hieab H
AU - Jian, Xueqiu
AU - Yang, Qiong
AU - Smith, Albert Vernon
AU - Bis, Joshua C
AU - Teumer, Alexander
AU - Scholz, Markus
AU - Armstrong, Nicola J
AU - Hofer, Edith
AU - Saba, Yasaman
AU - Luciano, Michelle
AU - Bernard, Manon
AU - Trompet, Stella
AU - Yang, Jingyun
AU - Gillespie, Nathan A
AU - van der Lee, Sven J
AU - Neumann, Alexander
AU - Ahmad, Shahzad
AU - Andreassen, Ole A
AU - Ames, David
AU - Amin, Najaf
AU - Arfanakis, Konstantinos
AU - Bastin, Mark E
AU - Becker, Diane M
AU - Beiser, Alexa S
AU - Beyer, Frauke
AU - Brodaty, Henry
AU - Bryan, R Nick
AU - Bülow, Robin
AU - Dale, Anders M
AU - De Jager, Philip L
AU - Deary, Ian J
AU - DeCarli, Charles
AU - Fleischman, Debra A
AU - Gottesman, Rebecca F
AU - van der Grond, Jeroen
AU - Gudnason, Vilmundur
AU - Harris, Tamara B
AU - Homuth, Georg
AU - Knopman, David S
AU - Kwok, John B
AU - Lewis, Cora E
AU - Li, Shuo
AU - Loeffler, Markus
AU - Lopez, Oscar L
AU - Maillard, Pauline
AU - El Marroun, Hanan
AU - Mather, Karen A
AU - Mosley, Thomas H
AU - Muetzel, Ryan L
AU - Nauck, Matthias
AU - Nyquist, Paul A
AU - Panizzon, Matthew S
AU - Pausova, Zdenka
AU - Psaty, Bruce M
AU - Rice, Ken
AU - Rotter, Jerome I
AU - Royle, Natalie
AU - Satizabal, Claudia L
AU - Schmidt, Reinhold
AU - Schofield, Peter R
AU - Schreiner, Pamela J
AU - Sidney, Stephen
AU - Stott, David J
AU - Thalamuthu, Anbupalam
AU - Uitterlinden, Andre G
AU - Valdés Hernández, Maria C
AU - Vernooij, Meike W
AU - Wen, Wei
AU - White, Tonya
AU - Witte, A Veronica
AU - Wittfeld, Katharina
AU - Wright, Margaret J
AU - Yanek, Lisa R
AU - Tiemeier, Henning
AU - Kremen, William S
AU - Bennett, David A
AU - Jukema, J Wouter
AU - Paus, Tomas
AU - Wardlaw, Joanna M
AU - Schmidt, Helena
AU - Sachdev, Perminder S
AU - Villringer, Arno
AU - Grabe, Hans Jörgen
AU - Longstreth, W T
AU - van Duijn, Cornelia M
AU - Launer, Lenore J
AU - Seshadri, Sudha
AU - Ikram, M Arfan
AU - Fornage, Myriam
PY - 2018/9/26
Y1 - 2018/9/26
N2 - The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
AB - The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
U2 - 10.1038/s41467-018-06234-w
DO - 10.1038/s41467-018-06234-w
M3 - Article
C2 - 30258056
VL - 9
SP - 3945
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
ER -