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

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  • 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
  • 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
  • Diane M. Becker
  • Alexa S. Beiser
  • Frauke Beyer
  • Henry Brodaty
  • R. Nick Bryan
  • Robin Bülow
  • Anders M. Dale
  • Philip L. De Jager
  • 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
  • Claudia L. Satizabal
  • Reinhold Schmidt
  • Peter R. Schofield
  • Pamela J. Schreiner
  • Stephen Sidney
  • David J. Stott
  • Anbupalam Thalamuthu
  • Andre G. Uitterlinden
  • 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
  • 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

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http://www.nature.com/articles/s41467-018-06234-w
Original languageEnglish
Article number3945
JournalNature Communications
Volume9
Issue number1
Early online date26 Sep 2018
DOIs
Publication statusE-pub ahead of print - 26 Sep 2018

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.

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