Evidence map›Paper›PMID 40175353›Full record

SynthesisNature communications2025

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, Daeun Shin, Eun Hye Lee and 10 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Review
  3. The Alzheimer's disease risk gene SORL1 is a regulator of excitatory neuronal function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Jun Pyo Kim *Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-4376-3107
Sang-Hyuk Jung *Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4116-3327
Beomjin JangDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.ORCID http://orcid.org/0009-0008-9056-1480
Minyoung ChoDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-5023-0902
Minku SongDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.
Jaeyoung KimDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-6983-7907
Beomsu KimDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-7410-4273
Hyunwoo LeeAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.ORCID http://orcid.org/0009-0003-7212-2162
Daeun ShinAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
Eun Hye LeeAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-4206-6214
Hyemin JangDepartment of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Bo-Hyun KimAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
Hongki HamDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0009-0002-0806-6453
Dokyoon KimDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4592-9564
Towfique RajRonald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-9355-5704
Carlos CruchagaDepartment of Psychiatry, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-0276-2899
Hee Jin KimAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
Duk L NaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-0098-7592
Sang Won SeoAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea. sangwonseo@empas.com.
Hong-Hee WonDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea. wonhh@skku.edu.ORCID http://orcid.org/0000-0001-5719-0552

Funding

Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Margaret Sewell · 2020 to 2026
$31.0M
Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs) RS-2020-KH106434Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs) RS-2022-KH125557Ministry of Health, Welfare and Family Affairs | Korea National Institute of Health (KNIH) 2023-ER1001-01Ministry of Health, Welfare and Family Affairs | Korea National Institute of Health (KNIH) 2024-ER1003-00Ministry of Science, ICT and Future Planning (MSIP) RS-2021-II212068National Research Foundation of Korea (NRF) RS-2019-NR040057National Research Foundation of Korea (NRF) RS-2023-00247408National Research Foundation of Korea (NRF) RS-2023-00262527National Research Foundation of Korea (NRF) RS-2024-00223277NIA NIH HHS P30 AG066514Sungkyunkwan University (Sung Kyun Kwan University) 2023 Postdoctoral Research Program
6 · The paper itself

Abstract

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.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBrainLDL-Receptor Related ProteinsMembrane Transport ProteinsAgedAllelesApolipoprotein E4East Asian PeopleEastern European PeopleFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMicrogliaAmyloid beta-PeptidesApolipoprotein E4LDL-Receptor Related ProteinsMembrane Transport ProteinsSORL1 protein, human

Identifiers

PMID40175353
PMCPMC11965558

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.