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

Author

Listed:
  • Dina Vojinovic

    (Erasmus MC University Medical Center)

  • Hieab H. Adams

    (Erasmus MC University Medical Center
    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
    Faculty of Medicine, University of Iceland)

  • Joshua C. Bis

    (University of Washington)

  • Alexander Teumer

    (University Medicine Greifswald)

  • Markus Scholz

    (University of Leipzig
    University of Leipzig)

  • Nicola J. Armstrong

    (Mathematics and Statistics, Murdoch University
    Centre for Healthy Brain Ageing, School of Psychiatry, UNSW)

  • Edith Hofer

    (Medical University of Graz
    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
    Leiden University Medical Center)

  • Jingyun Yang

    (Rush University Medical Center
    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
    University of Melbourne)

  • Najaf Amin

    (Erasmus MC University Medical Center)

  • Konstantinos Arfanakis

    (Rush University Medical Center
    Illinois Institute of Technology
    Rush University Medical Center)

  • Mark E. Bastin

    (University of Edinburgh
    University of Edinburgh
    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
    University of New South Wales)

  • 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
    Cell Circuits Program, Broad Institute)

  • Ian J. Deary

    (University of Edinburgh)

  • Charles DeCarli

    (University of California)

  • Debra A. Fleischman

    (Rush University Medical Center
    Rush University Medical Center
    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
    Faculty of Medicine, University of Iceland)

  • 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
    The University of Sydney)

  • Cora E. Lewis

    (The University of Alabama at Birmingham School of Medicine)

  • Shuo Li

    (Boston University)

  • Markus Loeffler

    (University of Leipzig
    University of Leipzig)

  • Oscar L. Lopez

    (University of Pittsburgh)

  • Pauline Maillard

    (University of California)

  • Hanan El Marroun

    (Erasmus University Medical Center Rotterdam
    Erasmus University Rotterdam)

  • Karen A. Mather

    (Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
    Neuroscience Research Australia Randwick)

  • Thomas H. Mosley

    (The University of Mississippi Medical Center)

  • Ryan L. Muetzel

    (Erasmus MC University Medical Center
    Erasmus University Medical Center Rotterdam)

  • 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
    University of Toronto)

  • Bruce M. Psaty

    (University of Washington
    University of Washington
    University of Washington
    Kaiser Permanente Washington Health Research Institute)

  • Ken Rice

    (University of Washington)

  • Jerome I. Rotter

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Natalie Royle

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Claudia L. Satizabal

    (Framingham Heart Study
    Boston University School of Medicine)

  • Reinhold Schmidt

    (Medical University of Graz)

  • Peter R. Schofield

    (University of New South Wales
    Neuroscience Research Australia Randwick)

  • 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
    University of Edinburgh
    University of Edinburgh)

  • Meike W. Vernooij

    (Erasmus MC University Medical Center
    Erasmus MC University Medical Center)

  • Wei Wen

    (Centre for Healthy Brain Ageing, School of Psychiatry, UNSW)

  • Tonya White

    (Erasmus MC University Medical Center
    Erasmus University Medical Center Rotterdam)

  • A. Veronica Witte

    (Max Planck Institute of Cognitive and Brain Sciences
    University of Leipzig)

  • 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
    Erasmus MC University Medical Center)

  • William S. Kremen

    (University of California, San Diego)

  • David A. Bennett

    (Rush University Medical Center
    Rush University Medical Center)

  • J. Wouter Jukema

    (Leiden University Medical Center
    Einthoven Laboratory for Experimental Vascular Medicine, LUMC)

  • Tomas Paus

    (Rotman Research Institute, Baycrest
    University of Toronto)

  • Joanna M. Wardlaw

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Helena Schmidt

    (Institute for Molecular biology and biochemistry)

  • Perminder S. Sachdev

    (Centre for Healthy Brain Ageing, School of Psychiatry, UNSW
    Prince of Wales Hospital)

  • Arno Villringer

    (Max Planck Institute of Cognitive and Brain Sciences
    University of Leipzig)

  • Hans Jörgen Grabe

    (German Center for Neurodegenerative Diseases (DZNE)
    University Medicine Greifswald)

  • W T Longstreth

    (University of Washington
    University of Washington)

  • Cornelia M. van Duijn

    (Erasmus MC University Medical Center
    University of Oxford)

  • Lenore J. Launer

    (National Institutes of Health)

  • Sudha Seshadri

    (Framingham Heart Study
    Boston University School of Medicine)

  • M Arfan Ikram

    (Erasmus MC University Medical Center
    Erasmus MC University Medical Center
    Erasmus MC University Medical Center)

  • Myriam Fornage

    (The University of Texas Health Science Center at Houston Institute of Molecular Medicine)

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.

Suggested Citation

  • 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 Lucian, 2018. "Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06234-w
    DOI: 10.1038/s41467-018-06234-w
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    Cited by:

    1. Marine Lanfranchi & Sozerko Yandiev & Géraldine Meyer-Dilhet & Salma Ellouze & Martijn Kerkhofs & Raphael Dos Reis & Audrey Garcia & Camille Blondet & Alizée Amar & Anita Kneppers & Hélène Polvèche & , 2024. "The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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