المؤلفون: Leonie Lampe, Peter R. Schofield, Hieab H.H. Adams, Mark A. Logue, Charles DeCarli, Wen Wei, Neda Jahanshad, Jose R. Romero, Anbupalam Thalamuth, Christophe Tzourio, Lloyd T. Elliott, Rui Xia, Meike W. Vernooij, Maria J. Knol, Jeroen van der Grond, Vilmundur Gudnason, Martin Dichigans, Karen A. Mather, Jonathan Marchini, John W Kwok, Jiyang Jain, Bernard Mazoyer, Rebecca F. Gottesman, Edith Hofer, Maragret J Wright, Nicola J. Armstrong, Christine Fennema-Notestine, Joanna M. Wardlaw, Thomas H. Mosley, Stella Trompet, Helena Schmidt, Clinton B. Wright, William S. Kremen, Paul A. Nyquist, Reinhold Schmidt, Stephanie Debbette, Michelle Luciano, Lenore J. Launer, Henry Brodaty, M Afran Ikram, Nicole D Deuker, Rainer Malik, Pauline Maillard, David Ames, J. Wouter Jukema, Cornelia M. van Duijn, Markus Scholz, Lukas Pirpamer, Ralph L. Sacco, Lisa R. Yanek, Julian N. Trollor, Siggi Siggurdsson, Qiong Yang, Muralidharan Sargurupremraj, Mark Jenkinson, Shuo Li, Ludovica Griffanti, Mark E. Bastin, Alexa S. Beiser, Fidel Alfaro-Almagro, David J. Stott, Veronica Witte, Perminder S. Sachdev, Moris Zoe, Asta L Haberg, Paul M. Thompson, Sudha Seshadri, Piyush G Gampwar, Albert V. Smith, Claudia L. Satizabal, Ian J. Deary, Arno Villringer, David C. Liewald, Myriam Fornage, Dina Vojinovic, Clifford R. Jack, Lewis C. Becker, Najaf Amin, Philippe Amouyel, Stephen M. Smith, Brian G. Kral, Gennady V. Roshchupkin, Matthias L. Schroeter

مصطلحات موضوعية: Genetics, White matter, Candidate gene, medicine.anatomical_structure, Genetic variation, Ischemic stroke, Etiology, medicine, Deep white matter hyperintensities, Locus (genetics), Disease, Biology

الوصف: 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.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd359fb4a98b9f246838be93682abc4e
https://doi.org/10.1101/683367