Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hofer, E; Cavalieri, M; Bis, JC; DeCarli, C; Fornage, M; Sigurdsson, S; Srikanth, V; Trompet, S; Verhaaren, BF; Wolf, C; Yang, Q; Adams, HH; Amouyel, P; Beiser, A; Buckley, BM; Callisaya, M; Chauhan, G; de Craen, AJ; Dufouil, C; van Duijn, CM; Ford, I; Freudenberger, P; Gottesman, RF; Gudnason, V; Heiss, G; Hofman, A; Lumley, T; Martinez, O; Mazoyer, B; Moran, C; Niessen, WJ; Phan, T; Psaty, BM; Satizabal, CL; Sattar, N; Schilling, S; Shibata, DK; Slagboom, PE; Smith, A; Stott, DJ; Taylor, KD; Thomson, R; Töglhofer, AM; Tzourio, C; van Buchem, M; Wang, J; Westendorp, RG; Windham, BG; Vernooij, MW; Zijdenbos, A; Beare, R; Debette, S; Ikram, MA; Jukema, JW; Launer, LJ; Longstreth, WT; Mosley, TH; Seshadri, S; Schmidt, H; Schmidt, R; Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.
Stroke. 2015; 46(11):3048-3057
Doi: 10.1161/STROKEAHA.115.009252
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- Führende Autor*innen der Med Uni Graz
- Hofer Edith
- Schmidt Reinhold
- Co-Autor*innen der Med Uni Graz
- Birkl-Töglhofer Anna Maria
- Cavalieri Margherita
- Freudenberger Paul
- Schmidt Helena
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- Abstract:
- White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10(-8)). Four loci were suggestive (P<1×10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10(-6)); 12q13.13 (rs4761974, P=8.71×10(-7)); 20p12.1 (rs6135309, P=3.69×10(-6)); and 4p15.31 (rs7664442, P=2.26×10(-6)). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors. © 2015 American Heart Association, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Cohort Studies -
- Disease Progression -
- Female -
- Genetic Predisposition to Disease - epidemiology
- Genetic Predisposition to Disease - genetics
- Genome-Wide Association Study - methods
- Humans -
- Leukoencephalopathies - diagnosis
- Leukoencephalopathies - epidemiology
- Leukoencephalopathies - genetics
- Male -
- Middle Aged -
- Prospective Studies -
- White Matter - pathology