Imperial College London
Alternate

Professor Paul M. Matthews

Faculty of Medicine, Department of Brain Sciences

Edmond and Lily Safra Chair, Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 2855p.matthews

 
 
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Assistant

 

Ms Siobhan Dillon +44 (0)20 7594 2855

 
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Location

 

E502Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sargurupremraj:2020:10.1038/s41467-020-19111-2,
author = {Sargurupremraj, M and Suzuki, H and Jian, X and Sarnowski, C and Evans, TE and Bis, JC and Eiriksdottir, G and Sakaue, S and Terzikhan, N and Habes, M and Zhao, W and Armstrong, NJ and Hofer, E and Yanek, LR and Hagenaars, SP and Kumar, RB and van, den Akker EB and McWhirter, RE and Trompet, S and Mishra, A and Saba, Y and Satizabal, CL and Beaudet, G and Petit, L and Tsuchida, A and Zago, L and Schilling, S and Sigurdsson, S and Gottesman, RF and Lewis, CE and Aggarwal, NT and Lopez, OL and Smith, JA and Valdés, Hernández MC and van, der Grond J and Wright, MJ and Knol, MJ and Dörr, M and Thomson, RJ and Bordes, C and Le, Grand Q and Duperron, M-G and Smith, AV and Knopman, DS and Schreiner, PJ and Evans, DA and Rotter, JI and Beiser, AS and Maniega, SM and Beekman, M and Trollor, J and Stott, DJ and Vernooij, MW and Wittfeld, K and Niessen, WJ and Soumaré, A and Boerwinkle, E and Sidney, S and Turner, ST and Davies, G and Thalamuthu, A and Völker, U and van, Buchem MA and Bryan, RN a},
doi = {10.1038/s41467-020-19111-2},
journal = {Nature Communications},
title = {Cerebral small vessel disease genomics and its implications across the lifespan},
url = {http://dx.doi.org/10.1038/s41467-020-19111-2},
volume = {11},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Sargurupremraj,M
AU  - Suzuki,H
AU  - Jian,X
AU  - Sarnowski,C
AU  - Evans,TE
AU  - Bis,JC
AU  - Eiriksdottir,G
AU  - Sakaue,S
AU  - Terzikhan,N
AU  - Habes,M
AU  - Zhao,W
AU  - Armstrong,NJ
AU  - Hofer,E
AU  - Yanek,LR
AU  - Hagenaars,SP
AU  - Kumar,RB
AU  - van,den Akker EB
AU  - McWhirter,RE
AU  - Trompet,S
AU  - Mishra,A
AU  - Saba,Y
AU  - Satizabal,CL
AU  - Beaudet,G
AU  - Petit,L
AU  - Tsuchida,A
AU  - Zago,L
AU  - Schilling,S
AU  - Sigurdsson,S
AU  - Gottesman,RF
AU  - Lewis,CE
AU  - Aggarwal,NT
AU  - Lopez,OL
AU  - Smith,JA
AU  - Valdés,Hernández MC
AU  - van,der Grond J
AU  - Wright,MJ
AU  - Knol,MJ
AU  - Dörr,M
AU  - Thomson,RJ
AU  - Bordes,C
AU  - Le,Grand Q
AU  - Duperron,M-G
AU  - Smith,AV
AU  - Knopman,DS
AU  - Schreiner,PJ
AU  - Evans,DA
AU  - Rotter,JI
AU  - Beiser,AS
AU  - Maniega,SM
AU  - Beekman,M
AU  - Trollor,J
AU  - Stott,DJ
AU  - Vernooij,MW
AU  - Wittfeld,K
AU  - Niessen,WJ
AU  - Soumaré,A
AU  - Boerwinkle,E
AU  - Sidney,S
AU  - Turner,ST
AU  - Davies,G
AU  - Thalamuthu,A
AU  - Völker,U
AU  - van,Buchem MA
AU  - Bryan,RN
AU  - Dupuis,J
AU  - Bastin,ME
AU  - Ames,D
AU  - Teumer,A
AU  - Amouyel,P
AU  - Kwok,JB
AU  - Bülow,R
AU  - Deary,IJ
AU  - Schofield,PR
AU  - Brodaty,H
AU  - Jiang,J
AU  - Tabara,Y
AU  - Setoh,K
AU  - Miyamoto,S
AU  - Yoshida,K
AU  - Nagata,M
AU  - Kamatani,Y
AU  - Matsuda,F
AU  - Psaty,BM
AU  - Bennett,DA
AU  - De,Jager PL
AU  - Mosley,TH
AU  - Sachdev,PS
AU  - Schmidt,R
AU  - Warren,HR
AU  - Evangelou,E
AU  - Trégouët,D-A
AU  - International,Network against Thrombosis INVENT Consortium
AU  - International,Headache Genomics Consortium IHGC
AU  - Ikram,MA
AU  - Wen,W
AU  - DeCarli,C
AU  - Srikanth,VK
AU  - Jukema,JW
AU  - Slagboom,EP
AU  - Kardia,SLR
AU  - Okada,Y
AU  - Mazoyer,B
AU  - Wardlaw,JM
AU  - Nyquist,PA
AU  - Mather,KA
AU  - Grabe,HJ
AU  - Schmidt,H
AU  - Van,Duijn CM
AU  - Gudnason,V
AU  - Longstreth,WT
AU  - Launer,LJ
AU  - Lathrop,M
AU  - Seshadri,S
AU  - Tzourio,C
AU  - Adams,HH
AU  - Matthews,PM
AU  - Fornage,M
AU  - Debette,S
DO  - 10.1038/s41467-020-19111-2
PY  - 2020///
SN  - 2041-1723
TI  - Cerebral small vessel disease genomics and its implications across the lifespan
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-020-19111-2
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33293549
UR  - http://hdl.handle.net/10044/1/85599
VL  - 11
ER  -
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