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Cerebral small vessel disease genomics and its implications across the lifespan

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Cerebral small vessel disease genomics and its implications across the lifespan
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
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  Data: urn:ISSN:2041-1723 ; Nature Communications, 11, 1, 6285
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  Data: 2020
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  Data: 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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  Data: https://hdl.handle.net/1959.4/unsworks_74672
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  Data: 10.1038/s41467-020-19111-2
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  Data: https://hdl.handle.net/1959.4/unsworks_74672<br />https://unsworks.unsw.edu.au/bitstreams/33a5750b-c45e-4cc7-a24b-462c3e6166fe/download<br />https://doi.org/10.1038/s41467-020-19111-2
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  Data: open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read
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            – D: 01
              M: 01
              Type: published
              Y: 2020
          Identifiers:
            – Type: issn-locals
              Value: edsbas
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              Value: edsbas.oa
          Titles:
            – TitleFull: urn:ISSN:2041-1723 ; Nature Communications, 11, 1, 6285
              Type: main
ResultId 1