Academic Journal
Cerebral small vessel disease genomics and its implications across the lifespan
| Τίτλος: | Cerebral small vessel disease genomics and its implications across the lifespan |
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| Συγγραφείς: | 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, de Andrade, M, Basu, S, Berr, C, Brody, JA, Chasman, DI, Dartigues, JF, Folsom, AR, Germain, M, Wen, Wei, Mather, Karen |
| Πηγή: | urn:ISSN:2041-1723 ; Nature Communications, 11, 1, 6285 |
| Στοιχεία εκδότη: | Springer Nature |
| Έτος έκδοσης: | 2020 |
| Συλλογή: | UNSW Sydney (The University of New South Wales): UNSWorks |
| Θεματικοί όροι: | 4202 Epidemiology, 31 Biological Sciences, 42 Health Sciences, 3105 Genetics, Acquired Cognitive Impairment, Clinical Trials and Supportive Activities, Biotechnology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Hypertension, Vascular Cognitive Impairment/Dementia, Clinical Research, Alzheimer's Disease Related Dementias (ADRD), Biomedical Imaging, Alzheimer's Disease, Cerebrovascular, Neurodegenerative, Aging, Prevention, Human Genome, Brain Disorders, Genetics, Cardiovascular, Neurosciences, Stroke, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, 80 and over |
| Περιγραφή: | 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. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | unknown |
| Relation: | https://hdl.handle.net/1959.4/unsworks_74672 |
| DOI: | 10.1038/s41467-020-19111-2 |
| Διαθεσιμότητα: | https://hdl.handle.net/1959.4/unsworks_74672 https://unsworks.unsw.edu.au/bitstreams/33a5750b-c45e-4cc7-a24b-462c3e6166fe/download https://doi.org/10.1038/s41467-020-19111-2 |
| Rights: | open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Αριθμός Καταχώρησης: | edsbas.5E08AF02 |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1038/s41467-020-19111-2 |
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