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

Nat Commun
Authors
Dina Vojinovic
Hieab Adams
Xueqiu Jian
Qiong Yang
Albert Smith
Joshua Bis
Alexander Teumer
Markus Scholz
Nicola Armstrong
Edith Hofer
Yasaman Saba
Michelle Luciano
Manon Bernard
Stella Trompet
Jingyun Yang
Nathan Gillespie
Sven Van der Lee
Alexander Neumann
Shahzad Ahmad
Ole Andreassen
David Ames
Najaf Amin
Konstantinos Arfanakis
Mark Bastin
Diane Becker
Alexa Beiser
Frauke Beyer
Henry Brodaty
R Nick Bryan
Robin Bülow
Anders Dale
Philip De Jager
Ian Deary
Charles DeCarli
Debra Fleischman
Rebecca Gottesman
Jeroen Van der Grond
Vilmundur Gudnason
Tamara Harris
Georg Homuth
David Knopman
John Kwok
Cora Lewis
Shuo Li
Markus Loeffler
Oscar Lopez
Pauline Maillard
Hanan Marroun
Karen Mather
Thomas Mosley
Ryan Muetzel
Matthias Nauck
Paul Nyquist
Matthew Panizzon
Zdenka Pausova
Bruce Psaty
Ken Rice
Jerome Rotter
Natalie Royle
Claudia Satizabal
Reinhold Schmidt
Peter Schofield
Pamela Schreiner
Stephen Sidney
David Stott
Anbupalam Thalamuthu
André Uitterlinden
Maria Hernández
Meike Vernooij
Wei Wen
Tonya White
A Veronica Witte
Katharina Wittfeld
Margaret Wright
Lisa Yanek
Henning Tiemeier
William Kremen
David Bennett
J Wouter Jukema
Tomáš Paus
Joanna Wardlaw
Helena Schmidt
Perminder Sachdev
Arno Villringer
Hans Grabe
W Longstreth
Cornelia van Duijn
Lenore Launer
Sudha Seshadri
M Arfan Ikram
Myriam Fornage
Keywords
Humans
Aged
Middle Aged
Genome-Wide Association Study
Genome, Human
Organ Size
Lateral Ventricles
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 (ρ = -0.59, p-value = 3.14 × 10), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
Year of Publication
2018
Journal
Nat Commun
Volume
9
Issue
1
Pages
3945
Date Published
2018 09 26
ISSN
2041-1723
DOI
10.1038/s41467-018-06234-w
PubMed ID
30258056
PubMed Central ID
PMC6158214
Links
Grant list
U01 HL096917 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
G0701120 / MRC_ / Medical Research Council / United Kingdom
U01 AG052409 / AG / NIA NIH HHS / United States
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 AG015819 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
MR/M013111/1 / MRC_ / Medical Research Council / United Kingdom
R01 AG017917 / AG / NIA NIH HHS / United States
G1001245 / MRC_ / Medical Research Council / United Kingdom
U01 HL096899 / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States

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