Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Dina Vojinovic; Hieab H Adams; Xueqiu Jian; Qiong Yang; Albert Vernon Smith; Joshua C Bis; Alexander Teumer; Markus Scholz; Nicola J Armstrong; Edith Hofer; Yasaman Saba; Michelle Luciano; Manon Bernard; Stella Trompet; Jingyun Yang; Nathan A Gillespie; Sven J van der Lee; Alexander Neumann; Shahzad Ahmad; Ole A Andreassen; David Ames; Najaf Amin; Konstantinos Arfanakis; Mark E Bastin; Diane M Becker; Alexa S Beiser; Frauke Beyer; Henry Brodaty; R Nick Bryan; Robin Bülow; Anders M Dale; Philip L De Jager; Ian J Deary; Charles DeCarli; Debra A Fleischman; Rebecca F Gottesman; Jeroen van der Grond; Vilmundur Gudnason; Tamara B Harris; Georg Homuth; David S Knopman; John B Kwok; Cora E Lewis; Shuo Li; Markus Loeffler; Oscar L Lopez; Pauline Maillard; Hanan El Marroun; Karen A Mather; Thomas H Mosley; Ryan L Muetzel; Matthias Nauck; Paul A Nyquist; Matthew S Panizzon; Zdenka Pausova; Bruce M Psaty; Ken Rice; Jerome I Rotter; Natalie Royle; Claudia L Satizabal; Reinhold Schmidt; Peter R Schofield; Pamela J Schreiner; Stephen Sidney; David J Stott; Anbupalam Thalamuthu; Andre G Uitterlinden; Maria C Valdés Hernández; Meike W Vernooij; Wei Wen; Tonya White; A Veronica Witte; Katharina Wittfeld; Margaret J Wright; Lisa R Yanek; Henning Tiemeier; William S Kremen; David A Bennett; J Wouter Jukema; Tomas Paus; Joanna M Wardlaw; Helena Schmidt; Perminder S Sachdev; Arno Villringer; Hans Jörgen Grabe; W T Longstreth; Cornelia M van Duijn; Lenore J Launer; Sudha Seshadri; M Arfan Ikram; Myriam Fornage

doi:10.1038/s41467-018-06234-w

Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Dina Vojinovic, Hieab H Adams, Xueqiu Jian, Qiong Yang, Albert Vernon Smith, Joshua C Bis, Alexander Teumer, Markus Scholz, Nicola J Armstrong, Edith Hofer, Yasaman Saba, Michelle Luciano, Manon Bernard, Stella Trompet, Jingyun Yang, Nathan A Gillespie, Sven J van der Lee, Alexander Neumann, Shahzad Ahmad, Ole A AndreassenDavid Ames, Najaf Amin, Konstantinos Arfanakis, Mark E Bastin, Diane M Becker, Alexa S Beiser, Frauke Beyer, Henry Brodaty, R Nick Bryan, Robin Bülow, Anders M Dale, Philip L De Jager, Ian J Deary, Charles DeCarli, Debra A Fleischman, Rebecca F Gottesman, Jeroen van der Grond, Vilmundur Gudnason, Tamara B Harris, Georg Homuth, David S Knopman, John B Kwok, Cora E Lewis, Shuo Li, Markus Loeffler, Oscar L Lopez, Pauline Maillard, Hanan El Marroun, Karen A Mather, Thomas H Mosley, Ryan L Muetzel, Matthias Nauck, Paul A Nyquist, Matthew S Panizzon, Zdenka Pausova, Bruce M Psaty, Ken Rice, Jerome I Rotter, Natalie Royle, Claudia L Satizabal, Reinhold Schmidt, Peter R Schofield, Pamela J Schreiner, Stephen Sidney, David J Stott, Anbupalam Thalamuthu, Andre G Uitterlinden, Maria C Valdés Hernández, Meike W Vernooij, Wei Wen, Tonya White, A Veronica Witte, Katharina Wittfeld, Margaret J Wright, Lisa R Yanek, Henning Tiemeier, William S Kremen, David A Bennett, J Wouter Jukema, Tomas Paus, Joanna M Wardlaw, Helena Schmidt, Perminder S Sachdev, Arno Villringer, Hans Jörgen Grabe, W T Longstreth, Cornelia M van Duijn, Lenore J Launer, Sudha Seshadri, M Arfan Ikram, Myriam Fornage

Neurology

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

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
Pages (from-to)	3945
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06234-w
Publication status	Published - 26 Sep 2018

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10.1038/s41467-018-06234-w

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Vojinovic, D., Adams, H. H., Jian, X., Yang, Q., Smith, A. V., Bis, J. C., ... Fornage, M. (2018). Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. Nature Communications, 9(1), 3945. https://doi.org/10.1038/s41467-018-06234-w

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. / Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 3945.

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title = "Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume",

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.",

author = "Dina Vojinovic and Adams, {Hieab H} and Xueqiu Jian and Qiong Yang and Smith, {Albert Vernon} and Bis, {Joshua C} and Alexander Teumer and Markus Scholz and Armstrong, {Nicola J} and Edith Hofer and Yasaman Saba and Michelle Luciano and Manon Bernard and Stella Trompet and Jingyun Yang and Gillespie, {Nathan A} and {van der Lee}, {Sven J} and Alexander Neumann and Shahzad Ahmad and Andreassen, {Ole A} and David Ames and Najaf Amin and Konstantinos Arfanakis and Bastin, {Mark E} and Becker, {Diane M} and Beiser, {Alexa S} and Frauke Beyer and Henry Brodaty and Bryan, {R Nick} and Robin B{\"u}low and Dale, {Anders M} and {De Jager}, {Philip L} and Deary, {Ian J} and Charles DeCarli and Fleischman, {Debra A} and Gottesman, {Rebecca F} and {van der Grond}, Jeroen and Vilmundur Gudnason and Harris, {Tamara B} and Georg Homuth and Knopman, {David S} and Kwok, {John B} and Lewis, {Cora E} and Shuo Li and Markus Loeffler and Lopez, {Oscar L} and Pauline Maillard and {El Marroun}, Hanan and Mather, {Karen A} and Mosley, {Thomas H} and Muetzel, {Ryan L} and Matthias Nauck and Nyquist, {Paul A} and Panizzon, {Matthew S} and Zdenka Pausova and Psaty, {Bruce M} and Ken Rice and Rotter, {Jerome I} and Natalie Royle and Satizabal, {Claudia L} and Reinhold Schmidt and Schofield, {Peter R} and Schreiner, {Pamela J} and Stephen Sidney and Stott, {David J} and Anbupalam Thalamuthu and Uitterlinden, {Andre G} and {Vald{\'e}s Hern{\'a}ndez}, {Maria C} and Vernooij, {Meike W} and Wei Wen and Tonya White and Witte, {A Veronica} and Katharina Wittfeld and Wright, {Margaret J} and Yanek, {Lisa R} and Henning Tiemeier and Kremen, {William S} and Bennett, {David A} and Jukema, {J Wouter} and Tomas Paus and Wardlaw, {Joanna M} and Helena Schmidt and Sachdev, {Perminder S} and Arno Villringer and Grabe, {Hans J{\"o}rgen} and Longstreth, {W T} and {van Duijn}, {Cornelia M} and Launer, {Lenore J} and Sudha Seshadri and Ikram, {M Arfan} and Myriam Fornage",

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Vojinovic, D, Adams, HH, Jian, X, Yang, Q, Smith, AV, Bis, JC, Teumer, A, Scholz, M, Armstrong, NJ, Hofer, E, Saba, Y, Luciano, M, Bernard, M, Trompet, S, Yang, J, Gillespie, NA, van der Lee, SJ, Neumann, A, Ahmad, S, Andreassen, OA, Ames, D, Amin, N, Arfanakis, K, Bastin, ME, Becker, DM, Beiser, AS, Beyer, F, Brodaty, H, Bryan, RN, Bülow, R, Dale, AM, De Jager, PL, Deary, IJ, DeCarli, C, Fleischman, DA, Gottesman, RF, van der Grond, J, Gudnason, V, Harris, TB, Homuth, G, Knopman, DS, Kwok, JB, Lewis, CE, Li, S, Loeffler, M, Lopez, OL, Maillard, P, El Marroun, H, Mather, KA, Mosley, TH, Muetzel, RL, Nauck, M, Nyquist, PA, Panizzon, MS, Pausova, Z, Psaty, BM, Rice, K, Rotter, JI, Royle, N, Satizabal, CL, Schmidt, R, Schofield, PR, Schreiner, PJ, Sidney, S, Stott, DJ, Thalamuthu, A, Uitterlinden, AG, Valdés Hernández, MC, Vernooij, MW, Wen, W, White, T, Witte, AV, Wittfeld, K, Wright, MJ, Yanek, LR, Tiemeier, H, Kremen, WS, Bennett, DA, Jukema, JW, Paus, T, Wardlaw, JM, Schmidt, H, Sachdev, PS, Villringer, A, Grabe, HJ, Longstreth, WT, van Duijn, CM, Launer, LJ, Seshadri, S, Ikram, MA & Fornage, M 2018, 'Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume', Nature Communications, vol. 9, no. 1, pp. 3945. https://doi.org/10.1038/s41467-018-06234-w

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 -