| Title: |
Cerebral small vessel disease genomics and its implications across the lifespan |
| Authors: |
Sargurupremraj, M. (Muralidharan); Suzuki, H. (Hideaki); Jian, X. (Xueqiu); Sarnowski, C.; Evans, T.E (Tavia); Bis, J.C. (Joshua); Eiriksdottir, G. (Gudny); Sakaue, S. (Saori); Terzikhan, N. (Natalie); Habes, M. (Mohamad); Zhao, W. (Wei); Armstrong, N.J. (Nicola J.); Hofer, E. (Edith); Yanek, L.R. (Lisa); Hagenaars, S.P. (Saskia P.); Kumar, R.B. (Rajan B.); Akker, E.B. (Erik) van den; McWhirter, R.E. (Rebekah E.); Trompet, S. (Stella); Mishra, A. (Aniket); Saba, Y. (Yasaman); Satizabal, C.L. (Claudia); Beaudet, G. (Gregory); Petit, L. (Laurent); Tsuchida, A. (Ami); Zago, L. (Laure); Schilling, S. (Sabrina); Sigurdsson, S. (Stefan); Gottesman, R.F. (Rebecca); Lewis, C.E. (Cora E.); Aggarwal, N.T. (Neelum T.); Lopez, O.L. (Oscar); Smith, J.A. (Jennifer A); Valdés Hernández, M.C. (Maria C.); van der Grond, J. (Jeroen); Wright, M.J. (Margaret); Knol, M.J. (Maria J.); Dörr, M. (Marcus); Thomson, R. (Russell); Bordes, C. (Constance); Le Grand, Q. (Quentin); Duperron, M.-G. (Marie-Gabrielle); Smith, A.V. (Albert); Knopman, D.S. (David); Schreiner, P.J. (Pamela); Evans, D.A. (Denis A.); Rotter, J.I. (Jerome I.); Beiser, A. (Alexa); Maniega, S.M. (Susana Muñoz); Beekman, M. (Marian); Trollor, J.; Stott, D.J. (David. J.); Vernooij, M.W. (Meike); Wittfeld, K. (Katharina); Niessen, W.J. (Wiro); Soumaré, A. (Aicha); Boerwinkle, E.A. (Eric); Sidney, S. (Stephen); Turner, S.T. (Stephen); Davies, G. (Gail); Thalamuthu, A. (Anbupalam); Völker, U. (Uwe); Buchem, M.A. (Mark) van; Bryan, R.N. (R. Nick); Amin, N. (Najaf); Bastin, M.E. (Mark); Ames, D.J. (David); Teumer, A. (Alexander); Amouyel, P. (Philippe); Kwok, J.B. (John B.); Bülow, R. (Robin); Deary, I.J. (Ian); Schofield, P.R. (Peter R.); Brodaty, H. (Henry); Jiang, J. (Jiyang); Tabara, Y. (Yasuharu); Setoh, K. (Kazuya); Miyamoto, S. (Susumu); Yoshida, K. (Kazumichi); Nagata, M. (Manabu); Kamatani, Y. (Yoichiro); Matsuda, F. (Fumihiko); Psaty, B.M. (Bruce); Bennett, D.A. (David); De Jager, P.; Mosley, T.H. (Thomas H.); Sachdev, P.S. (Perminder); Schmidt, R. (Reinhold); Warren, H. (Helen); Evangelou, E. (Evangelos); Trégouët, D.-A. (David-Alexandre); Andrade, M. (Mariza) de; Basu, S. (Saonli); Berr, C. (Claudine); Brody, J.A. (Jennifer A.); Chasman, D.I. (Daniel I.); Dartigues, J.-F.; Folsom, A.R. (Aaron); Germain, M. (Marine); de Haan, H. (Hugoline); Heit, J.A. (John); Houwing-Duitermaat, J. (Jeanine); Kabrhel, C. (Christopher); Kraft, P. (Peter); Legal, G. (Grégoire); Lindström, S. (Sara); Monajemi, R. (Ramin); Morange, P.-E. (P.); Psaty, B.M. (Bruce M.); Reitsma, P.H. (Pieter H.); Jarvelin, M.-R. (Marjo-Riitta); Rose, L.M. (Lynda M.); Peyvandi, F. (Flora); Saut, N. (Noemie); Slagboom, E. (Eline); Smadja, D. (David); Smith, N.L. (Nicholas L.); Suchon, P. (Pierre); Tang, W. (Weihong); Taylor, K.D. (Kent D.); Tregouet, D.-A. (David-Alexandre); Tzourio, C. (Christophe); Visser, M.C.H. (Marieke) de; Hylckama Vlieg, A. (Astrid) van; Weng, L.-C.; Wiggins, K.L. (Kerri L.); Gormley, A.M.; Anttila, V. (Verneri); Winsvold, B.S. (Bendik S.); Palta, P. (Priit); Esko, T. (Tõnu); Pers, T.H. (Tune H.); Farh, K.-H. (Kai-How); Cuenca-Leon, E. (Ester); Muona, M. (Mikko); Furlotte, N.A. (Nicholas A.); Kurth, T. (Tobias); Ingason, A. (Andres); McMahon, G. (George); Ligthart, L. (Lannie); Terwindt, G.M. (Gisela M.); Todt, U. (Unda); Freilinger, T.M. (Tobias M.); Ran, C. (Caroline); Gordon, S.G. (Scott G.); Stam, A.H. (Anine); Steinberg, S. (Stacy); Borck, G. (Guntram); Koiranen, M. (Markku); Quaye, L. (Lydia); Adams, H.H.H. (Hieab H. H.); Lehtimäki, T. (Terho); Sarin, A.-P.; Wedenoja, J. (Juho); Hinds, D.A. (David A.); Buring, J.E. (Julie); Schürks, M. (Markus); Ridker, P.M. (Paul M.); Gudlaug Hrafnsdottir, M. (Maria); Stefansson, H. (Hreinn); Ring, S.M. (Susan M.); Hottenga, J.J. (Jouke Jan); Penninx, B.W.J.H. (Brenda); Färkkilä, M. (Markus); Artto, V. (Ville); Kaunisto, M.A. (Mari); Vepsäläinen, S. (Salli); Malik, R. (Rainer); Heath, A.C. (Andrew); Madden, P.A.F. (Pamela A. F.); Martin, N.G. (Nicholas); Montgomery, G.W. (Grant); Kurki, M. (Mitja); Kals, M. (Mart); Mägi, R. (Reedik); Pärn, K. (Kalle); Hämäläinen, E. (Eija); Huang, H. (Hailiang); Byrnes, A.E. (Andrea E.); Franke, L. (Lude); Huang, J. (Jie); Stergiakouli, E. (Evie); Lee, P.H. (Phil H.); Sandor, C. (Cynthia); Webber, C. (Caleb); Cader, Z. (Zameel); Müller-Myhsok, B. (B.); Schreiber, S. (Stefan); Meitinger, T. (Thomas); Hagen, K. (Knut); Salomaa, V. (Veikko); Heikkilä, K. (Kauko); Loehrer, E. (Elizabeth); Uitterlinden, A.G. (André); Hofman, A. (Albert); Duijn, C.M. (Cornelia) van; Cherkas, L. (Lynn); Pedersen, L.M. (Linda M.); Stubhaug, A. (Audun); Nielsen, C.S. (Christopher S.); Männikkö, M. (Minna); Mihailov, E. (Evelin); Milani, L. (Lili); Esserlind, A.-L. (Ann-Louise); Francke Christensen, A. (Anne); Folkmann Hansen, T. (Thomas); Werge, T. (Thomas); Kaprio, J. (Jaakko); Aromaa, A. (Arpo); Raitakari, O. (Olli); Ikram, M.A. (M. Arfan); Spector, T.D. (Timothy); Järvelin, M.-R. (Marjo-Riitta); Metspalu, A. (Andres); Kubisch, C. (Christian); Beckmann, J.S. (Jacques); Ferrari, M.D. (Michel); Belin, A.C. (Andrea C.); Wessman, M. (Maija); van den Maagdenberg, A.M.J.M. (Arn M. J. M.); Zwart, J-A. (John-Anker); Boomsma, D.I. (Dorret); Davey Smith, G. (George); Eriksson, N. (Nicholas); Daly, M.J. (Mark); Neale, B.M. (Benjamin); Olesen, J. (Jes); Chasman, D.I. (Daniel); Nyholt, D.R. (Dale); Palotie, A. (Aarno); Ikram, M.A. (Arfan); Wen, W. (Wei); DeCarli, C. (Charles); Srikanth, V. (Velandai); Jukema, J.W. (Jan Wouter); Slagboom, P.E. (Eline); Kardia, S.L.R. (Sharon); Okada, Y. (Yukinori); Mazoyer, B. (Bernard); Wardlaw, J.M. (J.); Nyquist, P. (Paul); Mather, R.; Grabe, H.J. (Hans Jörgen); Schmidt, H. (Helena); Van Duijn, C.M. (Cornelia M.); Gudnason, V. (Vilmundur); Longstreth Jr, W.T.; Launer, L.J. (Lenore); Lathrop, M. (Mark); Seshadri, S. (Sudha); Adams, H.H.H. (Hieab); Matthews, P.M. (P.); Fornage, M. (Myriam); Debette, S. (Stéphanie) |
| Source: |
Nature Communications vol. 11 no. 1 |
| Publication Year: |
2020 |
| Collection: |
RePub - Publications from Erasmus University, Rotterdam |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://repub.eur.nl/pub/132445; urn:hdl:1765/132445 |
| DOI: |
10.1038/s41467-020-19111-2 |
| Availability: |
https://repub.eur.nl/pub/132445; https://doi.org/10.1038/s41467-020-19111-2 |
| Accession Number: |
edsbas.A6CD8009 |
| Database: |
BASE |