White matter hyperintensities partly mediate genetically predicted blood pressure effects on vascular dementia
Hwang S.. Research Square, 2026-10-05
Topic: Genetics and APOE
Background White matter hyperintensities (WMH) mark cerebral small vessel disease and sit on the path from hypertension to vascular dementia (VaD). Prior Mendelian randomization in European ancestry has linked blood pressure (BP) to WMH. We tested whether that association replicates in Japanese ancestry and whether WMH captures part of the genetically predicted BP effect on VaD after a priori APOE exclusion. Methods Two-sample Mendelian randomization used European genome-wide association studies of BP, WMH, and VaD, with Japanese replication of BP residual to WMH residual. The primary estimator was random-effects inverse-variance weighted analysis. Two-step Mendelian randomization multiplied each APOE -excluded BP to WMH estimate by the APOE -excluded WMH to VaD log-odds ratio. Results Genetically predicted diastolic and systolic BP associated with higher WMH in Europeans (β = 0.176 and 0.091 WMH SD per 10 mm Hg). The same direction replicated in Japanese ancestry on a residual-SD scale. Pulse pressure did not. Diastolic and systolic BP associated with VaD (odds ratios 1.36 and 1.12). Both had an indirect path through WMH (indirect odds ratios 1.10 and 1.05). The descriptive mediated proportion was 0.31 for diastolic BP. The systolic proportion interval included 0. Conclusions Genetically predicted BP raises WMH in European and Japanese ancestry. Diastolic and systolic BP have an indirect path through WMH to VaD. A descriptive mediated proportion whose interval excludes 0 is limited to diastolic BP.
Key findings
- Results Genetically predicted diastolic and systolic BP associated with higher WMH in Europeans (β = 0.176 and 0.091 WMH SD per 10 mm Hg).
- Diastolic and systolic BP associated with VaD (odds ratios 1.36 and 1.12).
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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. Check the citation against the original before you use it.
APA 7th
Hwang, S. (2026). White matter hyperintensities partly mediate genetically predicted blood pressure effects on vascular dementia. Research Square. https://doi.org/10.21203/rs.3.rs-11236498/v1
Vancouver
Hwang S. White matter hyperintensities partly mediate genetically predicted blood pressure effects on vascular dementia. Research Square. 2026. doi:10.21203/rs.3.rs-11236498/v1.
BibTeX
@article{hwang2026-c2ebe340,
author = {Hwang, S.},
title = {{White matter hyperintensities partly mediate genetically predicted blood pressure effects on vascular dementia}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-11236498/v1},
url = {https://doi.org/10.21203/rs.3.rs-11236498/v1}
}