Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Cerebral small vessel disease genomics and its implications across the lifespan

Muralidharan Sargurupremraj, Hideaki Suzuki, Xueqiu Jian, Chloé Sarnowski, Tavia E. Evans, Joshua C. Bis, Gudny Eiriksdottir, Saori Sakaue, Natalie Terzikhan, Mohamad Habes, Wei Zhao, Nicola J. Armstrong, Edith Hofer, Lisa R. Yanek, Saskia P. Hagenaars, Rajan B. Kumar, Erik B. van den Akker, Rebekah McWhirter, Stella Trompet, Aniket Mishra, Yasaman Saba, Claudia L. Satizábal, Grégory Beaudet, Laurent Petit, Ami Tsuchida, Laure Zago, Sabrina Schilling, Sigurður Sigurðsson, Rebecca F. Gottesman, Cora E. Lewis, Neelum T. Aggarwal, Oscar L. López, Jennifer A. Smith, Maria C. Valdés Hernández, Jeroen van der Grond, Margaret J. Wright, Maria J. Knol, Marcus Dörr, Russell Thomson, Constance Bordes, Quentin Le Grand, Marie‐Gabrielle Duperron, Albert V. Smith, David S. Knopman, Pamela J. Schreiner, Denis A. Evans, Jerome I. Rotter, Alexa Beiser, Susana Muñoz Maniega, Marian Beekman, Julian N. Trollor, David J. Stott, Meike W. Vernooij, Katharina Wittfeld, Wiro J. Niessen, Aïcha Soumaré, Eric Boerwinkle, Stephen Sidney, Stephen T. Turner, Gail Davies, Anbupalam Thalamuthu, Uwe Völker, Mark A. van Buchem, R. Nick Bryan, Josée Dupuis, Mark E. Bastin, David Ames, Alexander Teumer, Philippe Amouyel, John B. Kwok, Robin Bülow, Ian J. Deary, Peter R. Schofield, Henry Brodaty, Jiyang Jiang, Yasuharu Tabara, Kazuya Setoh, Susumu Miyamoto, Kazumichi Yoshida, Manabu Nagata, Yoichiro Kamatani, Fumihiko Matsuda, Bruce M. Psaty, David A. Bennett, Philip L. De Jager, Thomas H. Mosley, Perminder S. Sachdev, Reinhold Schmidt, Helen R. Warren, Εvangelos Εvangelou, David‐Alexandre Trégouët, Philippe Amouyel, Mariza de Andrade, Saonli Basu, Claudine Berr, Jennifer A. Brody, Daniel I. Chasman, Jean‐François Dartigues, Aaron R. Folsom, Marine Germain

Nature Communications · 2020

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Summary

This large international genomic study identified 27 loci associated with white matter hyperintensity burden, a marker of cerebral small vessel disease, and provided evidence that genetic risk variants influence white matter integrity across the lifespan. Mendelian randomization analyses suggested causal relationships between increasing WMH volume and stroke and Alzheimer-type dementia risk, whilst also revealing blood-pressure-independent biological pathways underlying small vessel disease. The findings support genetic stratification of high-risk individuals and identification of potential drug targets for preventive intervention trials.

UK applicability

The findings are relevant to UK clinical practice and research, as cerebral small vessel disease contributes significantly to stroke and dementia burden in ageing populations. However, the study is primarily mechanistic and genomic; direct translation to UK primary or secondary prevention strategies would require prospective validation and health economic assessment in UK populations.

Key measures

WMH volume (primary outcome); white matter integrity in young adults; associations with stroke and Alzheimer-type dementia; blood pressure relationships; expression of 39 genes with 4 encoding known drug targets

Outcomes reported

The study identified 27 genome-wide loci associated with white matter hyperintensity (WMH) volume in 50,970 older individuals and examined lifetime genetic impacts on brain white matter integrity and clinical outcomes including stroke and dementia risk.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Observational cohort with Mendelian randomization and transcriptome-wide colocalization analyses
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41467-020-19111-2
Catalogue ID
SNmohdwfqs-dvwns4

Topic tags

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