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.; 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.; 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; Marroun, Hanan El; 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.; Hernández, Maria C. Valdés; 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

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. 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. 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 and Myriam Fornage ()
Additional contact information
Dina Vojinovic: Erasmus MC University Medical Center
Hieab H. Adams: Erasmus MC University Medical Center
Xueqiu Jian: The University of Texas Health Science Center at Houston Institute of Molecular Medicine
Qiong Yang: Boston University
Albert Vernon Smith: Icelandic Heart Association
Joshua C. Bis: University of Washington
Alexander Teumer: University Medicine Greifswald
Markus Scholz: University of Leipzig
Nicola J. Armstrong: Mathematics and Statistics, Murdoch University
Edith Hofer: Medical University of Graz
Yasaman Saba: Institute for Molecular biology and biochemistry
Michelle Luciano: University of Edinburgh
Manon Bernard: Research Institute of the Hospital for Sick Children
Stella Trompet: Leiden University Medical Center
Jingyun Yang: Rush University Medical Center
Nathan A. Gillespie: Virginia Commonwealth University
Sven J. Lee: Erasmus MC University Medical Center
Alexander Neumann: Erasmus University Medical Center Rotterdam
Shahzad Ahmad: Erasmus MC University Medical Center
Ole A. Andreassen: University of Oslo
David Ames: National Ageing Research Institute
Najaf Amin: Erasmus MC University Medical Center
Konstantinos Arfanakis: Rush University Medical Center
Mark E. Bastin: University of Edinburgh
Diane M. Becker: Johns Hopkins School of Medicine
Alexa S. Beiser: Boston University
Frauke Beyer: Max Planck Institute of Cognitive and Brain Sciences
Henry Brodaty: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
R. Nick Bryan: The University of Texas at Austin Dell Medical School
Robin Bülow: University Medicine Greifswald
Anders M. Dale: University of California, San Diego
Philip L. Jager: Columbia University Medical Center
Ian J. Deary: University of Edinburgh
Charles DeCarli: University of California
Debra A. Fleischman: Rush University Medical Center
Rebecca F. Gottesman: Johns Hopkins School of Medicine
Jeroen van der Grond: Leiden University Medical Center
Vilmundur Gudnason: Icelandic Heart Association
Tamara B. Harris: National Institutes of Health
Georg Homuth: University Medicine Greifswald
David S. Knopman: Mayo Clinic
John B. Kwok: University of New South Wales
Cora E. Lewis: The University of Alabama at Birmingham School of Medicine
Shuo Li: Boston University
Markus Loeffler: University of Leipzig
Oscar L. Lopez: University of Pittsburgh
Pauline Maillard: University of California
Hanan El Marroun: Erasmus University Medical Center Rotterdam
Karen A. Mather: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
Thomas H. Mosley: The University of Mississippi Medical Center
Ryan L. Muetzel: Erasmus MC University Medical Center
Matthias Nauck: University Medicine Greifswald
Paul A. Nyquist: Johns Hopkins School of Medicine
Matthew S. Panizzon: University of California, San Diego
Zdenka Pausova: Research Institute of the Hospital for Sick Children
Bruce M. Psaty: University of Washington
Ken Rice: University of Washington
Jerome I. Rotter: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Natalie Royle: University of Edinburgh
Claudia L. Satizabal: Framingham Heart Study
Reinhold Schmidt: Medical University of Graz
Peter R. Schofield: University of New South Wales
Pamela J. Schreiner: University of Minnesota School of Public Health
Stephen Sidney: Kaiser Permanente Northern California Division of Research
David J. Stott: University of Glasgow
Anbupalam Thalamuthu: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
Andre G. Uitterlinden: Erasmus MC University Medical Center
Maria C. Valdés Hernández: University of Edinburgh
Meike W. Vernooij: Erasmus MC University Medical Center
Wei Wen: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
Tonya White: Erasmus MC University Medical Center
A. Veronica Witte: Max Planck Institute of Cognitive and Brain Sciences
Katharina Wittfeld: German Center for Neurodegenerative Diseases (DZNE)
Margaret J. Wright: University of Queensland
Lisa R. Yanek: Johns Hopkins School of Medicine
Henning Tiemeier: Erasmus University Medical Center Rotterdam
William S. Kremen: University of California, San Diego
David A. Bennett: Rush University Medical Center
J. Wouter Jukema: Leiden University Medical Center
Tomas Paus: Rotman Research Institute, Baycrest
Joanna M. Wardlaw: University of Edinburgh
Helena Schmidt: Institute for Molecular biology and biochemistry
Perminder S. Sachdev: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
Arno Villringer: Max Planck Institute of Cognitive and Brain Sciences
Hans Jörgen Grabe: German Center for Neurodegenerative Diseases (DZNE)
W T Longstreth: University of Washington
Cornelia M. van Duijn: Erasmus MC University Medical Center
Lenore J. Launer: National Institutes of Health
Sudha Seshadri: Framingham Heart Study
M Arfan Ikram: Erasmus MC University Medical Center
Myriam Fornage: The University of Texas Health Science Center at Houston Institute of Molecular Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06234-w

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