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Genome-wide association study of neuropathological features in Lewy body disease
Rebecca R. Valentino, Shunsuke Koga, Alexandra I. Soto‐Beasley, Daisuke Ono, Mikolaj A. Wieczorek, Patrick W. Johnson, Launia J. White, Molly M. Watkins et al.. Brain, 2025-03-14
Topic: Brain proteins, microglia and lab models
APOE ε4) was associated with a greater severity of each of Braak NFT stage [odds ratio (OR) = 3.07, P = 2.34 × 10-32], Thal amyloid phase (OR = 3.57, P = 3.28 × 10-29) and LBD subtype (OR = 1.78, P = 9.85 × 10-9), with similar findings observed in the independent replication series (Braak NFT stage, OR = 2.30, P = 2.70 × 10-11; Thal amyloid phase, OR = 3.17, P = 6.39 × 10-18; LBD subtype, OR = 2.68, P = 3.85 × 10-10). Although additional genome-wide significant associations were identified in the discovery series between LINC01581/MCTP2 rs547411734 and lower middle frontal LB counts, between TLE3 rs3743309 and lower cingulate LB counts, and between GRIN2A/ATF7IP2 rs1097915 and lower parahippocampal LB counts, these findings were not observed in the replication series. Our results indicate that the APOE ε4 allele is the most prominent genetic determinant of severity of neuropathology in LBD. These findings represent a key step forward in our understanding of genetic drivers of neuropathological features in LBD. Future studies utilizing meta-analytical approaches will be important to more precisely assess other associations that were not quite genome-wide significant in the discovery series.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Valentino, R. R., Koga, S., Soto‐Beasley, A. I., Ono, D., Wieczorek, M. A., Johnson, P. W., et al. (2025). Genome-wide association study of neuropathological features in Lewy body disease. Brain. https://doi.org/10.1093/brain/awaf105
Vancouver
Valentino RR, Koga S, Soto‐Beasley AI, Ono D, Wieczorek MA, Johnson PW, et al. Genome-wide association study of neuropathological features in Lewy body disease. Brain. 2025. doi:10.1093/brain/awaf105. PMID: 40091616.
BibTeX
@article{valentino2025-40091616,
author = {Valentino, Rebecca R. and Koga, Shunsuke and Soto‐Beasley, Alexandra I. and Ono, Daisuke and Wieczorek, Mikolaj A. and Johnson, Patrick W. and White, Launia J. and Watkins, Molly M. and others},
title = {{Genome-wide association study of neuropathological features in Lewy body disease}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awaf105},
pmid = {40091616},
url = {https://doi.org/10.1093/brain/awaf105}
}
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.
Key findings
- APOE ε4) was associated with a greater severity of each of Braak NFT stage [odds ratio (OR) = 3.07, P = 2.34 × 10-32], Thal amyloid phase (OR = 3.57, P = 3.28 × 10-29) and LBD subtype (OR = 1.78, P = 9.85 × 10-9), with similar findings observed in the independent replication series (Braak NFT stage, OR = 2.30, P = 2.70 × 10-11; Thal amyloid phase, OR = 3.17, P = 6.39 × 10-18; LBD subtype, OR = 2.68, P = 3.85 × 10-10).
- Although additional genome-wide significant associations were identified in the discovery series between LINC01581/MCTP2 rs547411734 and lower middle frontal LB counts, between TLE3 rs3743309 and lower cingulate LB counts, and between GRIN2A/ATF7IP2 rs1097915 and lower parahippocampal LB counts, these findings were not observed in the replication series.
- Our results indicate that the APOE ε4 allele is the most prominent genetic determinant of severity of neuropathology in LBD.
- These findings represent a key step forward in our understanding of genetic drivers of neuropathological features in LBD.
- Future studies utilizing meta-analytical approaches will be important to more precisely assess other associations that were not quite genome-wide significant in the discovery series.
Why it matters
This genome-wide association study found that the APOE ε4 allele was the most prominent genetic determinant of severity of neuropathology in Lewy body disease, while other associations were not confirmed in the replication series. It does not test any treatment or prevention, so it mainly adds to understanding of genetic drivers rather than offering a cure.
Study details
- Participants980
- Effect sizeOR = 3.57; OR = 1.78; OR = 2.30
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty journal. Scored zero for study design and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 980 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Owen A. Ross: h-index 95 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40091616) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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