Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI
Verhaaren BF, Debette S, Bis JC, Smith JA, Ikram MK, Adams HH, Beecham AH, Rajan KB et al.. Circulation. Cardiovascular genetics, 2015-02-07
Topic: Brain proteins, microglia and lab models
Background The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and results We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Verhaaren, B. F., Debette, S., Bis, J. C., Smith, J. A., Ikram, M. K., Adams, H. H., et al. (2015). Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI. Circulation. Cardiovascular genetics. https://doi.org/10.1161/circgenetics.114.000858
Vancouver
Verhaaren BF, Debette S, Bis JC, Smith JA, Ikram MK, Adams HH, et al. Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI. Circulation. Cardiovascular genetics. 2015. doi:10.1161/circgenetics.114.000858. PMID: 25663218.
BibTeX
@article{verhaaren2015-25663218,
author = {Verhaaren, B. F. and Debette, S. and Bis, J. C. and Smith, J. A. and Ikram, M. K. and Adams, H. H. and Beecham, A. H. and Rajan, K. B. and others},
title = {{Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI}},
journal = {Circulation. Cardiovascular genetics},
year = {2015},
doi = {10.1161/circgenetics.114.000858},
pmid = {25663218},
url = {https://doi.org/10.1161/circgenetics.114.000858}
}
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Key findings
- Background The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death.
- Methods and results We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent.
Why it matters
This large multiethnic genetic analysis identified several genetic loci associated with white matter hyperintensities on MRI, a marker linked to higher risk of stroke, dementia, and death. It concerns genetic influences on a brain marker, not treatment or prevention of Alzheimer's disease.
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Study details
- Study designmeta-analysis
- Participants17
- Evidence strengthHigh
How this study scored 69/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Circulation. Cardiovascular genetics) |
| Journal's citation record | 1 / 4 | Circulation Cardiovascular Genetics: journal h-index 114 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 17 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 5 / 7 | Cited 176 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 12.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Sudha S. Seshadri: h-index 148 (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 68 institution(s) in 11 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25663218) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.1161/circgenetics.114.000858
- PubMed: 25663218
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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