Cerebral small vessel disease genomics and its implications across the lifespan
Sargurupremraj M, Suzuki H, Jian X, Sarnowski C, Evans TE, Bis JC, Eiriksdottir G, Sakaue S et al.. Nature communications, 2020-12-08
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
Why it matters
In 50,970 older adults, this genetic study found 27 locations in the genome linked to white matter hyperintensities, the most common brain-scan sign of small vessel disease. The same risk variants were already tied to altered white matter in 1,738 young healthy adults (p = 2.5×10⁻⁷), which suggests this genetic risk acts across the lifespan. Genetic causal-inference (Mendelian randomization) analyses suggested that larger white-matter-lesion volume is linked to stroke and Alzheimer-type dementia, and higher blood pressure to larger lesion volume, even in people without diagnosed hypertension. These are genetic associations: the study points to drug targets worth testing in prevention trials but did not test any treatment.
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Study details
- Evidence strengthModerate
Limitations
This is a genetic-association study; it identifies genetic locations statistically linked to white matter damage but does not by itself show what these genes do biologically or whether the effect seen in young adults will lead to disease later in life.
How this study scored 70/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies (from PubMed type “Meta-Analysis”) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 5 / 7 | Cited 204 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.5 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 7.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 126 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Marine Germain: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 79 institution(s) in 10 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33293549) |
| Free to read | 2 / 2 | Free to read |
| Total | 70 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-020-19111-2
- PubMed: 33293549
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Sargurupremraj, M., Suzuki, H., Jian, X., Sarnowski, C., Evans, T. E., Bis, J. C., et al. (2020). Cerebral small vessel disease genomics and its implications across the lifespan. Nature communications. https://doi.org/10.1038/s41467-020-19111-2
Vancouver
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. doi:10.1038/s41467-020-19111-2. PMID: 33293549.
BibTeX
@article{sargurupremraj2020-33293549,
author = {Sargurupremraj, M. and Suzuki, H. and Jian, X. and Sarnowski, C. and Evans, T. E. and Bis, J. C. and Eiriksdottir, G. and Sakaue, S. and others},
title = {{Cerebral small vessel disease genomics and its implications across the lifespan}},
journal = {Nature communications},
year = {2020},
doi = {10.1038/s41467-020-19111-2},
pmid = {33293549},
url = {https://doi.org/10.1038/s41467-020-19111-2}
}
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