5
IRUS TotalDownloads
Altmetric
Cerebral small vessel disease genomics and its implications across the lifespan
| File | Description | Size | Format | |
|---|---|---|---|---|
 Cerebral small vessel disease genomics and its implications across the lifespan.pdf | Published version | 2.97 MB | Adobe PDF | View/Open |
| Title: | Cerebral small vessel disease genomics and its implications across the lifespan |
| Authors: | 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, M-G 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, D-A 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 |
| Item Type: | Journal Article |
| 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. |
| Issue Date: | 8-Dec-2020 |
| Date of Acceptance: | 10-Sep-2020 |
| URI: | http://hdl.handle.net/10044/1/85599 |
| DOI: | 10.1038/s41467-020-19111-2 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Research |
| Journal / Book Title: | Nature Communications |
| Volume: | 11 |
| Copyright Statement: | © The Author(s) 2020. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics WHITE-MATTER HYPERINTENSITIES WIDE ASSOCIATION MENDELIAN RANDOMIZATION BLOOD-PRESSURE COGNITIVE IMPAIRMENT GENETIC ARCHITECTURE AGING RESEARCH CELL-TYPES METAANALYSIS RISK Adult Aged Aged, 80 and over Alzheimer Disease Cerebral Small Vessel Diseases Diffusion Tensor Imaging Female Genetic Loci Genome-Wide Association Study Humans Hypertension Male Medical History Taking Mendelian Randomization Analysis Middle Aged Risk Assessment Risk Factors Stroke White Matter Young Adult International Network against Thrombosis (INVENT) Consortium International Headache Genomics Consortium (IHGC) Humans Alzheimer Disease Hypertension Medical History Taking Risk Assessment Risk Factors Adult Aged Aged, 80 and over Middle Aged Female Male Stroke Genome-Wide Association Study Young Adult Diffusion Tensor Imaging Genetic Loci Mendelian Randomization Analysis Cerebral Small Vessel Diseases White Matter |
| Publication Status: | Published |
| Conference Place: | England |
| Article Number: | 6285 |
| Online Publication Date: | 2020-12-08 |
| Appears in Collections: | Faculty of Medicine School of Public Health Department of Brain Sciences |
This item is licensed under a Creative Commons License
