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Common genetic variation indicates separate etiologies for periventricular and deep white matter hyperintensities
By
Nicola J. Armstrong,
Karen A. Mather,
Muralidharan Sargurupremraj,
Maria J. Knol,
Rainer Malik,
Claudia Satizabal,
Lisa R. Yanek,
Wei Wen,
Vilmundur Gudnason,
Nicole D Dueker,
Lloyd T Elliott,
Edith Hofer,
Neda Jahanshad,
Shuo Li,
Mark A Logue,
Michelle Luciano,
Markus Scholz,
Albert V Smith,
Stella S Trompet,
Dina Vojinovic,
Rui Xia,
Fidel Alfaro-Almagro,
David Ames,
Najaf Amin,
Philippe Amouyel,
Alexa S. Beiser,
Henry Brodaty,
Ian J Deary,
Christine Fennema-Notestine,
Piyush G Gampawar,
Rebecca F. Gottesman,
Ludovica Griffanti,
Clifford R. Jack,
Mark Jenkinson,
Jiyang Jiang,
Brian G Kral,
John Kwok,
Leonie Lampe,
David CM Liewald,
Pauline Maillard,
Jonathan Marchini,
Mark E Bastin,
Bernard Mazoyer,
Lukas Pirpamer,
Jose Rafael Romero,
Gennady V Roshchupkin,
Peter Schofield,
Matthias L Schroeter,
David J. Stott,
Anbupalam Thalamuthu,
Julian Trollor,
Christophe Tzourio,
Jeroen van der Grond,
Meike W Vernooij,
A. Veronica Witte,
Margaret J Wright,
Qiong Yang,
Morris Zoe,
Siggi Siggurdsson,
Arno Villringer,
Helena Schmidt,
Asta K. Haberg,
Cornelia M. van Duijn,
J Wouter Jukema,
Martin Dichgans,
Ralph L Sacco,
Clinton B Wright,
William S Kremen,
Lewis C. Becker,
Paul M Thompson,
Lenore Launer,
Thomas H Mosley,
Joanna M Wardlaw,
M Arfan Ikram,
Hieab HH Adams,
Reinhold Schmidt,
Stephen M. Smith,
Charles DeCarli,
Perminder S. Sachdev,
Myriam Fornage,
Stephanie Debette,
Sudha Seshadri,
Paul A Nyquist
Posted 27 Jun 2019
bioRxiv DOI: 10.1101/683367
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.
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