RT Journal Article
SR Electronic
T1 Common genetic variation indicates separate etiologies for periventricular and deep white matter hyperintensities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 683367
DO 10.1101/683367
A1 Nicola J Armstrong
A1 Karen A Mather
A1 Muralidharan Sargurupremraj
A1 Maria J Knol
A1 Rainer Malik
A1 Claudia L Satizabal
A1 Lisa R Yanek
A1 Wen Wei
A1 Vilmundur Gudnason
A1 Nicole D Deuker
A1 Lloyd T Elliott
A1 Edith Hofer
A1 Neda Jahanshad
A1 Shuo Li
A1 Mark A Logue
A1 Michelle Luciano
A1 Markus Scholz
A1 Albert Smith
A1 Stella S Trompet
A1 Dina Vojinovic
A1 Rui Xia
A1 Fidel Alfaro-Almagro
A1 David Ames
A1 Najaf Amin
A1 Philippe Amouyel
A1 Alexa S Beiser
A1 Henry Brodaty
A1 Ian J Deary
A1 Christine Fennema-Notestine
A1 Piyush G Gampwar
A1 Rebecca Gottesman
A1 Ludovica Griffanti
A1 Clifford R Jack
A1 Mark Jenkinson
A1 Jiyang Jain
A1 Brian G Kral
A1 John W Kwok
A1 Leonie Lampe
A1 David CM Liewald
A1 Pauline Maillard
A1 Jonathan Marchini
A1 Mark E Bastin
A1 Bernard Mazoyer
A1 Lukas Pirpamer
A1 José Rafael Romero
A1 Gennady V Roshchupkin
A1 Peter R Schofield
A1 Matthias L Schroeter
A1 David J Stott
A1 Anbupalam Thalamuth
A1 Julian Trollor
A1 Christophe Tzourio
A1 Jeroen van der Grond
A1 Meike W Vernooij
A1 Veronica A Witte
A1 Maragret J Wright
A1 Qiong Yang
A1 Moris Zoe
A1 Siggi Siggurdsson
A1 Arno Villringer
A1 Helena Schmidt
A1 Asta L Haberg
A1 Cornelia M Van Duijn
A1 J Wouter Jukema
A1 Martin Dichigans
A1 Ralph L Sacco
A1 Clinton B Wright
A1 William S Kremen
A1 Lewis C Becker
A1 Paul M Thompson
A1 Lenore Launer
A1 Thomas H Mosley
A1 Joanna M Wardlaw
A1 M Afran Ikram
A1 Hieab HH Adams
A1 Reinhold Schmidt
A1 Stephen M Smith
A1 Charles Decarli
A1 Perminder S Sachdev
A1 Myriam Fornage
A1 Stephanie Debbette
A1 Sudha Seshadri
A1 Paul A Nyquist
YR 2019
UL http://biorxiv.org/content/early/2019/06/27/683367.abstract
AB We conducted a genome-wide association meta-analysis of two ischemic white matter disease subtypes in the brain, periventricular and deep white matter hyperintensities (PVWMH and DWMH). In 26,654 participants, we found 10 independent genome-wide significant loci only associated with PVWMH, four of which have not been described previously for total WMH burden (16q24.2, 17q21.31, 10q23.1, 7q36.1). Additionally, in both PVWMH and DWMH we observed the previous association of the 17q25.1 locus with total WMH. We found that both phenotypes have shared but also distinct genetic architectures, consistent with both different underlying and related pathophysiology. PVWMH had more extensive genetic overlap with small vessel ischemic stroke, and unique associations with several loci implicated in ischemic stroke. DWMH were characterized by associations with loci previously implicated in vascular as well as astrocytic and neuronal function. Our study confirms the utility of these phenotypes and identifies new candidate genes associated only with PVWMH.