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Sargurupremraj, M.* ; Suzuki, H.* ; Jian, X.* ; Sarnowski, C.* ; Evans, T.E.* ; Bis, J.C.* ; Eiriksdottir, G.* ; Sakaue, S.* ; Terzikhan, N.* ; Habes, M.* ; Zhao, W.* ; Armstrong, N.J.* ; Hofer, E.* ; Yanek, L.R.* ; Hagenaars, S.P.* ; Kumar, R.B.* ; van den Akker, E.B.* ; McWhirter, R.E.* ; Trompet, S.* ; Mishra, A.* ; Saba, Y.* ; Satizabal, C.L.* ; Beaudet, G.* ; Petit, L.* ; Tsuchida, A.* ; Zago, L.* ; Schilling, S.* ; Sigurdsson, S.* ; Gottesman, R.F.* ; Lewis, C.E.* ; Aggarwal, N.T.* ; Lopez, O.L.* ; Smith, J.A.* ; Valdés Hernández, M.C.* ; van der Grond, J.* ; Wright, M.J.* ; Knol, M.J.* ; Dörr, M.* ; Thomson, R.J.* ; Bordes, C.* ; Le Grand, Q.* ; Duperron, M.G.* ; Smith, A.V.* ; Knopman, D.S.* ; Schreiner, P.J.* ; Evans, D.A.* ; Rotter, J.I.* ; Beiser, A.S.* ; Maniega, S.M.* ; Beekman, M.* ; Trollor, J.* ; Stott, D.J.* ; Vernooij, M.W.* ; Wittfeld, K.* ; Niessen, W.J.* ; Soumaré, A.* ; Boerwinkle, E.* ; Sidney, S.* ; Turner, S.T.* ; Davies, G.* ; Thalamuthu, A.* ; Völker, U.* ; van Buchem, M.A.* ; Bryan, R.N.* ; Dupuis, J.* ; Bastin, M.E.* ; Ames, D.* ; Teumer, A.* ; Amouyel, P.* ; Kwok, J.B.* ; Bülow, R.* ; Deary, I.J.* ; Schofield, P.R.* ; Brodaty, H.* ; Jiang, J.* ; Tabara, Y.* ; Setoh, K.* ; Miyamoto, S.* ; Yoshida, K.* ; Nagata, M.* ; Kamatani, Y.* ; Matsuda, F.* ; Psaty, B.M.* ; Bennett, D.A.* ; de Jager, P.L.* ; Mosley, T.H.* ; Sachdev, P.S.* ; Schmidt, R.* ; Warren, H.R.* ; Evangelou, E.* ; Trégouët, D.A.* ; Ikram, M.A.* ; Wen, W.* ; Decarli, C.* ; Srikanth, P.* ; Jukema, J.W.* ; Slagboom, E.* ; Kardia, S.L.R.* ; Okada, Y.* ; Mazoyer, B.* ; Wardlaw, J.M.* ; Nyquist, P.A.* ; Mather, K.A.* ; Grabe, H.J.* ; Schmidt, H.* ; van Duijn, C.M.* ; Gudnason, V.* ; Longstreth Jr, W.T.* ; Launer, L.J.* ; Lathrop, M* ; Seshadri, S* ; Tzourio, C.* ; Adams, H.H.* ; Matthews, P.M.* ; Fornage, M.* ; Debette, S.* ; International Headache Genomics Consortium (Meitinger, T.)

Cerebral small vessel disease genomics and its implications across the lifespan.

Nat. Commun. 11:6285 (2020)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 6285 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
DOI 10.1038/s41467-020-19111-2
Scopus ID 85097295783
PubMed ID 33293549
Erfassungsdatum 2020-12-17
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