Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Verhaaren, BF; Debette, S; Bis, JC; Smith, JA; Ikram, MK; Adams, HH; Beecham, AH; Rajan, KB; Lopez, LM; Barral, S; van Buchem, MA; van der Grond, J; Smith, AV; Hegenscheid, K; Aggarwal, NT; de Andrade, M; Atkinson, EJ; Beekman, M; Beiser, AS; Blanton, SH; Boerwinkle, E; Brickman, AM; Bryan, RN; Chauhan, G; Chen, CP; Chouraki, V; de Craen, AJ; Crivello, F; Deary, IJ; Deelen, J; De Jager, PL; Dufouil, C; Elkind, MS; Evans, DA; Freudenberger, P; Gottesman, RF; Guðnason, V; Habes, M; Heckbert, SR; Heiss, G; Hilal, S; Hofer, E; Hofman, A; Ibrahim-Verbaas, CA; Knopman, DS; Lewis, CE; Liao, J; Liewald, DC; Luciano, M; van der Lugt, A; Martinez, OO; Mayeux, R; Mazoyer, B; Nalls, M; Nauck, M; Niessen, WJ; Oostra, BA; Psaty, BM; Rice, KM; Rotter, JI; von Sarnowski, B; Schmidt, H; Schreiner, PJ; Schuur, M; Sidney, SS; Sigurdsson, S; Slagboom, PE; Stott, DJ; van Swieten, JC; Teumer, A; Töglhofer, AM; Traylor, M; Trompet, S; Turner, ST; Tzourio, C; Uh, HW; Uitterlinden, AG; Vernooij, MW; Wang, JJ; Wong, TY; Wardlaw, JM; Windham, BG; Wittfeld, K; Wolf, C; Wright, CB; Yang, Q; Zhao, W; Zijdenbos, A; Jukema, JW; Sacco, RL; Kardia, SL; Amouyel, P; Mosley, TH; Longstreth, WT; DeCarli, CC; van Duijn, CM; Schmidt, R; Launer, LJ; Grabe, HJ; Seshadri, SS; Ikram, MA; Fornage, M.
Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.
Circ Cardiovasc Genet. 2015; 8(2):398-409
Doi: 10.1161/CIRCGENETICS.114.000858
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Birkl-Töglhofer Anna Maria
- Freudenberger Paul
- Hofer Edith
- Schmidt Helena
- Schmidt Reinhold
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms. © 2015 American Heart Association, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Aged, 80 and over -
- Chromosomes, Human - genetics
- Continental Population Groups -
- Female -
- Genetic Loci -
- Genome-Wide Association Study -
- Humans -
- Male -
- Meta-Analysis as Topic -
- Middle Aged -
- Models, Genetic -
- Stroke - ethnology
- Stroke - genetics
- Stroke - pathology
- White Matter -
- Find related publications in this database (Keywords)
- cerebral small vessel diseases
- cerebrovascular disorders
- genome-wide association study
- hypertension
- leukoencephalopathies
- polymorphisms, single nucleotide