Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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Sargurupremraj, M; Suzuki, H; Jian, X; Sarnowski, C; Evans, TE; Bis, JC; Eiriksdottir, G; Sakaue, S; Terzikhan, N; Habes, M; Zhao, W; Armstrong, NJ; Hofer, E; Yanek, LR; Hagenaars, SP; Kumar, RB; van den Akker, EB; McWhirter, RE; Trompet, S; Mishra, A; Saba, Y; Satizabal, CL; Beaudet, G; Petit, L; Tsuchida, A; Zago, L; Schilling, S; Sigurdsson, S; Gottesman, RF; Lewis, CE; Aggarwal, NT; Lopez, OL; Smith, JA; Valdés Hernández, MC; van der Grond, J; Wright, MJ; Knol, MJ; Dörr, M; Thomson, RJ; Bordes, C; Le Grand, Q; Duperron, MG; Smith, AV; Knopman, DS; Schreiner, PJ; Evans, DA; Rotter, JI; Beiser, AS; Maniega, SM; Beekman, M; Trollor, J; Stott, DJ; Vernooij, MW; Wittfeld, K; Niessen, WJ; Soumaré, A; Boerwinkle, E; Sidney, S; Turner, ST; Davies, G; Thalamuthu, A; Völker, U; van Buchem, MA; Bryan, RN; Dupuis, J; Bastin, ME; Ames, D; Teumer, A; Amouyel, P; Kwok, JB; Bülow, R; Deary, IJ; Schofield, PR; Brodaty, H; Jiang, J; Tabara, Y; Setoh, K; Miyamoto, S; Yoshida, K; Nagata, M; Kamatani, Y; Matsuda, F; Psaty, BM; Bennett, DA; De Jager, PL; Mosley, TH; Sachdev, PS; Schmidt, R; Warren, HR; Evangelou, E; Trégouët, DA; International Network against Thrombosis (INVENT) Consortium; International Headache Genomics Consortium (IHGC); Ikram, MA; Wen, W; DeCarli, C; Srikanth, VK; Jukema, JW; Slagboom, EP; Kardia, SLR; Okada, Y; Mazoyer, B; Wardlaw, JM; Nyquist, PA; Mather, KA; Grabe, HJ; Schmidt, H; Van Duijn, CM; Gudnason, V; Longstreth, WT; Launer, LJ; Lathrop, M; Seshadri, S; Tzourio, C; Adams, HH; Matthews, PM; Fornage, M; Debette, S.
Cerebral small vessel disease genomics and its implications across the lifespan.
Nat Commun. 2020; 11(1):6285-6285
Doi: 10.1038/s41467-020-19111-2
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- Co-Autor*innen der Med Uni Graz
- Hofer Edith
- SABA Yasaman
- Schmidt Helena
- Schmidt Reinhold
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- Abstract:
- White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Alzheimer Disease - epidemiology
- Alzheimer Disease - genetics
- Cerebral Small Vessel Diseases - complications
- Cerebral Small Vessel Diseases - diagnosis
- Cerebral Small Vessel Diseases - genetics
- Diffusion Tensor Imaging -
- Female -
- Genetic Loci -
- Genome-Wide Association Study -
- Humans -
- Hypertension - epidemiology
- Hypertension - genetics
- Male -
- Medical History Taking -
- Mendelian Randomization Analysis -
- Middle Aged -
- Risk Assessment -
- Risk Factors -
- Stroke - epidemiology
- Stroke - genetics
- White Matter - diagnostic imaging
- Young Adult -