Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition
Jun Pyo Kim, Sang-Hyuk Jung, Beomjin Jang, Minyoung Cho, Minku Song, Jaeyoung Kim, Beomsu Kim, Hyunwoo Lee et al.. Nature communications, 2025-04-02
Topic: Genetics and APOE
GWAS of Alzheimer's disease have been predominantly based on European ancestry cohorts with clinically diagnosed patients. Increasing the ancestral diversity of GWAS and focusing on imaging brain biomarkers for Alzheimer's disease may lead to the identification of new genetic loci. Here, we perform a GWAS on cerebral β-amyloid deposition measured by PET imaging in 3,885 East Asians and a cross-ancestry GWAS meta-analysis with data from 11,816 European participants. Our GWAS analysis replicates known loci (APOE4, CR1, and FERMT2) and identifies a novel locus near SORL1 that is significantly associated with β-amyloid deposition. Single-nucleus expression analysis shows that SORL1 is differentially expressed according to β-amyloid positivity in microglia. Our joint association analysis using the SORL1 lead variant (rs76490923) and the APOE4 allele demonstrates that the risk of β-amyloid deposition is reduced by up to 43.5% in APOE4 non-carriers and up to 55.6% in APOE4 carriers, according to the allelic dosage of the rs76490923 T allele. Our findings suggest that SORL1 may play an important role in the pathogenesis of Alzheimer's disease, particularly in relation to β-amyloid deposition.
Key findings
- Our GWAS analysis replicates known loci (APOE4, CR1, and FERMT2) and identifies a novel locus near SORL1 that is significantly associated with β-amyloid deposition.
- Our findings suggest that SORL1 may play an important role in the pathogenesis of Alzheimer's disease, particularly in relation to β-amyloid deposition.
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Study details
- Study designmeta-analysis
- Effect size43.5%; 55.6%
- Evidence strengthHigh
How this study scored 79/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size and studied in people because the record does not state it. We have no data on journal's citation record, 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, multi-centre collaboration and free to read, so those were left out: it earned 44 of the 56 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 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 | 2 / 2 | Indexed in PubMed (PMID 40175353) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 44 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 44 of the 56 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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APA 7th
Kim, J. P., Jung, S.-H., Jang, B., Cho, M., Song, M., Kim, J., et al. (2025). Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition. Nature communications. https://doi.org/10.1038/s41467-025-57751-4
Vancouver
Kim JP, Jung S.-H, Jang B, Cho M, Song M, Kim J, et al. Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition. Nature communications. 2025. doi:10.1038/s41467-025-57751-4. PMID: 40175353.
BibTeX
@article{kim2025-40175353,
author = {Kim, Jun Pyo and Jung, Sang-Hyuk and Jang, Beomjin and Cho, Minyoung and Song, Minku and Kim, Jaeyoung and Kim, Beomsu and Lee, Hyunwoo and others},
title = {{Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition}},
journal = {Nature communications},
year = {2025},
doi = {10.1038/s41467-025-57751-4},
pmid = {40175353},
url = {https://doi.org/10.1038/s41467-025-57751-4}
}
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