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

TitleGenome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume.
Publication TypeJournal Article
Year of Publication2018
AuthorsVojinovic D, Adams HH, Jian X, Yang Q, Smith A V, 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 NR, 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, Marroun HEl, 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, Hernández MCValdés, Vernooij MW, Wen W, White T, A Witte V, Wittfeld K, Wright MJ, Yanek LR, Tiemeier H, Kremen WS, Bennett DA, J Jukema W, Paus T, Wardlaw JM, Schmidt H, Sachdev PS, Villringer A, Grabe HJörgen, Longstreth WT, van Duijn CM, Launer LJ, Seshadri S, M Ikram A
Secondary AuthorsFornage M
JournalNat Commun
Volume9
Issue1
Pagination3945
Date Published2018 09 26
ISSN2041-1723
KeywordsAged, Genome, Human, Genome-Wide Association Study, Humans, Lateral Ventricles, Middle Aged, Organ Size
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.

DOI10.1038/s41467-018-06234-w
Alternate JournalNat Commun
PubMed ID30258056
PubMed Central IDPMC6158214
Grant ListR01 AG054076 / AG / NIA NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS 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 HL096814 / HL / NHLBI NIH HHS / United States
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
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