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Cerebral small vessel disease genomics and its implications across the lifespan. / Sargurupremraj, Muralidharan; Suzuki, Hideaki; Jian, Xueqiu; Sarnowski, Chloé; Evans, Tavia E.; Bis, Joshua C.; Eiriksdottir, Gudny; Sakaue, Saori; Terzikhan, Natalie; Habes, Mohamad; Zhao, Wei; Armstrong, Nicola J.; Hofer, Edith; Yanek, Lisa R.; Hagenaars, Saskia P.; Kumar, Rajan B.; van den Akker, Erik B.; McWhirter, Rebekah E.; Trompet, Stella; Mishra, Aniket; Saba, Yasaman; Satizabal, Claudia L.; Beaudet, Gregory; Petit, Laurent; Tsuchida, Ami; Zago, Laure; Schilling, Sabrina; Sigurdsson, Sigurdur; Gottesman, Rebecca F.; Lewis, Cora E.; Aggarwal, Neelum T.; Lopez, Oscar L.; Smith, Jennifer A.; Valdés Hernández, Maria C.; van der Grond, Jeroen; Wright, Margaret J.; Knol, Maria J.; Dörr, Marcus; Thomson, Russell J.; Bordes, Constance; Le Grand, Quentin; Duperron, Marie Gabrielle; Smith, Albert V.; Niessen, Wiro J.; Pers, Tune H.; Ingason, Andres; Francke Christensen, Anne; Folkmann Hansen, Thomas; Werge, Thomas; Olesen, Jes; International Network against Thrombosis (INVENT) Consortium; International Headache Genomics Consortium (IHGC).
In:
Nature Communications, Vol. 11, No. 1, 6285, 2020.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
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, Niessen, WJ
, Pers, TH, Ingason, A, Francke Christensen, A
, Folkmann Hansen, T, Werge, T, Olesen, J, International Network against Thrombosis (INVENT) Consortium & International Headache Genomics Consortium (IHGC) 2020, '
Cerebral small vessel disease genomics and its implications across the lifespan',
Nature Communications, vol. 11, no. 1, 6285.
https://doi.org/10.1038/s41467-020-19111-2APA
Sargurupremraj, M., Suzuki, H., Jian, X., Sarnowski, C., Evans, T. E., Bis, J. C., Eiriksdottir, G., Sakaue, S., Terzikhan, N., Habes, M., Zhao, W., Armstrong, N. J., Hofer, E., Yanek, L. R., Hagenaars, S. P., Kumar, R. B., van den Akker, E. B., McWhirter, R. E., Trompet, S., ... International Headache Genomics Consortium (IHGC) (2020).
Cerebral small vessel disease genomics and its implications across the lifespan.
Nature Communications,
11(1), [6285].
https://doi.org/10.1038/s41467-020-19111-2Vancouver
Sargurupremraj M, Suzuki H, Jian X, Sarnowski C, Evans TE, Bis JC et al.
Cerebral small vessel disease genomics and its implications across the lifespan.
Nature Communications. 2020;11(1). 6285.
https://doi.org/10.1038/s41467-020-19111-2Author
Sargurupremraj, Muralidharan ; Suzuki, Hideaki ; Jian, Xueqiu ; Sarnowski, Chloé ; Evans, Tavia E. ; Bis, Joshua C. ; Eiriksdottir, Gudny ; Sakaue, Saori ; Terzikhan, Natalie ; Habes, Mohamad ; Zhao, Wei ; Armstrong, Nicola J. ; Hofer, Edith ; Yanek, Lisa R. ; Hagenaars, Saskia P. ; Kumar, Rajan B. ; van den Akker, Erik B. ; McWhirter, Rebekah E. ; Trompet, Stella ; Mishra, Aniket ; Saba, Yasaman ; Satizabal, Claudia L. ; Beaudet, Gregory ; Petit, Laurent ; Tsuchida, Ami ; Zago, Laure ; Schilling, Sabrina ; Sigurdsson, Sigurdur ; Gottesman, Rebecca F. ; Lewis, Cora E. ; Aggarwal, Neelum T. ; Lopez, Oscar L. ; Smith, Jennifer A. ; Valdés Hernández, Maria C. ; van der Grond, Jeroen ; Wright, Margaret J. ; Knol, Maria J. ; Dörr, Marcus ; Thomson, Russell J. ; Bordes, Constance ; Le Grand, Quentin ; Duperron, Marie Gabrielle ; Smith, Albert V. ; Niessen, Wiro J. ; Pers, Tune H. ; Ingason, Andres ; Francke Christensen, Anne ; Folkmann Hansen, Thomas ; Werge, Thomas ; Olesen, Jes ; International Network against Thrombosis (INVENT) Consortium ; International Headache Genomics Consortium (IHGC). / Cerebral small vessel disease genomics and its implications across the lifespan. In: Nature Communications. 2020 ; Vol. 11, No. 1.
Bibtex
@article{3a7eb7ed0d694b13a2d1a64728c11e9e,
title = "Cerebral small vessel disease genomics and its implications across the lifespan",
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.",
author = "Muralidharan Sargurupremraj and Hideaki Suzuki and Xueqiu Jian and Chlo{\'e} Sarnowski and Evans, {Tavia E.} and Bis, {Joshua C.} and Gudny Eiriksdottir and Saori Sakaue and Natalie Terzikhan and Mohamad Habes and Wei Zhao and Armstrong, {Nicola J.} and Edith Hofer and Yanek, {Lisa R.} and Hagenaars, {Saskia P.} and Kumar, {Rajan B.} and {van den Akker}, {Erik B.} and McWhirter, {Rebekah E.} and Stella Trompet and Aniket Mishra and Yasaman Saba and Satizabal, {Claudia L.} and Gregory Beaudet and Laurent Petit and Ami Tsuchida and Laure Zago and Sabrina Schilling and Sigurdur Sigurdsson and Gottesman, {Rebecca F.} and Lewis, {Cora E.} and Aggarwal, {Neelum T.} and Lopez, {Oscar L.} and Smith, {Jennifer A.} and {Vald{\'e}s Hern{\'a}ndez}, {Maria C.} and {van der Grond}, Jeroen and Wright, {Margaret J.} and Knol, {Maria J.} and Marcus D{\"o}rr and Thomson, {Russell J.} and Constance Bordes and {Le Grand}, Quentin and Duperron, {Marie Gabrielle} and Smith, {Albert V.} and Niessen, {Wiro J.} and Pers, {Tune H.} and Andres Ingason and {Francke Christensen}, Anne and {Folkmann Hansen}, Thomas and Thomas Werge and Jes Olesen and {International Network against Thrombosis (INVENT) Consortium} and {International Headache Genomics Consortium (IHGC)}",
year = "2020",
doi = "10.1038/s41467-020-19111-2",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",
}
RIS
TY - JOUR
T1 - Cerebral small vessel disease genomics and its implications across the lifespan
AU - Sargurupremraj, Muralidharan
AU - Suzuki, Hideaki
AU - Jian, Xueqiu
AU - Sarnowski, Chloé
AU - Evans, Tavia E.
AU - Bis, Joshua C.
AU - Eiriksdottir, Gudny
AU - Sakaue, Saori
AU - Terzikhan, Natalie
AU - Habes, Mohamad
AU - Zhao, Wei
AU - Armstrong, Nicola J.
AU - Hofer, Edith
AU - Yanek, Lisa R.
AU - Hagenaars, Saskia P.
AU - Kumar, Rajan B.
AU - van den Akker, Erik B.
AU - McWhirter, Rebekah E.
AU - Trompet, Stella
AU - Mishra, Aniket
AU - Saba, Yasaman
AU - Satizabal, Claudia L.
AU - Beaudet, Gregory
AU - Petit, Laurent
AU - Tsuchida, Ami
AU - Zago, Laure
AU - Schilling, Sabrina
AU - Sigurdsson, Sigurdur
AU - Gottesman, Rebecca F.
AU - Lewis, Cora E.
AU - Aggarwal, Neelum T.
AU - Lopez, Oscar L.
AU - Smith, Jennifer A.
AU - Valdés Hernández, Maria C.
AU - van der Grond, Jeroen
AU - Wright, Margaret J.
AU - Knol, Maria J.
AU - Dörr, Marcus
AU - Thomson, Russell J.
AU - Bordes, Constance
AU - Le Grand, Quentin
AU - Duperron, Marie Gabrielle
AU - Smith, Albert V.
AU - Niessen, Wiro J.
AU - Pers, Tune H.
AU - Ingason, Andres
AU - Francke Christensen, Anne
AU - Folkmann Hansen, Thomas
AU - Werge, Thomas
AU - Olesen, Jes
AU - International Network against Thrombosis (INVENT) Consortium
AU - International Headache Genomics Consortium (IHGC)
PY - 2020
Y1 - 2020
N2 - 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.
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.
U2 - 10.1038/s41467-020-19111-2
DO - 10.1038/s41467-020-19111-2
M3 - Journal article
C2 - 33293549
AN - SCOPUS:85097295783
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6285
ER -
