Evidence map›Paper›PMID 37198259›Full record

SynthesisMolecular psychiatry2023

Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease.

Julie Lake, Caroline Warly Solsberg, Jonggeol Jeffrey Kim, Juliana Acosta-Uribe, Mary B Makarious, Zizheng Li, Kristin Levine, Peter Heutink, Chelsea X Alvarado, Dan Vitale and 10 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 6 pooled it
–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

68 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
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  7. Article
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  11. Cross-ancestry polygenic risk scores enhance Alzheimer's disease risk prediction in multiethnic cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  13. Review
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  15. Article
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8 more citing papers are in PubMed but not listed here.

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.

Julie Lake *Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Caroline Warly Solsberg *Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7049-6281
Jonggeol Jeffrey KimLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Juliana Acosta-UribeNeuroscience Research Institute and the department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.ORCID 0000-0001-9978-093X
Mary B MakariousLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Zizheng LiPharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6953-7733
Kristin LevineData Tecnica International LLC, Washington, DC, USA.
Peter HeutinkAlector, Inc. 131 Oyster Point Blvd, Suite 600, South San Francisco, CA, 94080, USA.ORCID 0000-0001-5218-1737
Chelsea X AlvaradoLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Dan VitaleLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Sarang KangGwangju Alzheimer's disease and Related Dementia Cohort Research Center, Chosun University, Gwangju, 61452, Korea.
Jungsoo GimGwangju Alzheimer's disease and Related Dementia Cohort Research Center, Chosun University, Gwangju, 61452, Korea.
Kun Ho LeeGwangju Alzheimer's disease and Related Dementia Cohort Research Center, Chosun University, Gwangju, 61452, Korea.ORCID 0000-0003-4144-8162
Stefanie D Pina-EscuderoPharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA, USA.
Luigi FerrucciLongitudinal Studies Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-6273-1613
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Cornelis BlauwendraatCenter for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-9358-8111
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Jennifer S Yokoyama *Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7274-2634
Hampton L Leonard *Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. leonardhl@nih.gov.ORCID 0000-0003-2390-8110

Funding

Harmonized Data-Derived Resources for the Alzheimer's Disease and Related Dementias CommunityZIAAG000534 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2019 to 2025
$85.1M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Center for Alzheimer's and Related Dementias (CARD): Collaboration with the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat)ZIAAG000548 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2023 to 2025
$15.3M
Tau Metabolism in FTD: From Gene Mutations to Molecular Chaperones and Lysosomal ProteasesU54NS123985 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAO, AIMEE · 2021 to 2025
$9.0M
US-South American Initiative for Genetic-Neural-Behavioral Interactions in Human Neurodegenerative ResearchR01AG057234 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Claudia Duran-Aniotz, Agustin M. Ibanez · 2019 to 2026
$6.1M
The Aging Genome Association Study "AGE-GAIN"ZIAAG000965 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$4.0M
Elucidating clinical heterogeneity in early-onset AD via genomics, transcriptomics, and neuroimagingR01AG062588 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2019 to 2023
$4.0M
Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
Intramural NIH HHS Z01 AG000949Intramural NIH HHS ZIA NS003154NIA NIH HHS P30 AG062422NIA NIH HHS R01 AG057234NIA NIH HHS R01 AG062588NINDS NIH HHS U54 NS123985
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer's disease and related dementias.

Indexed as

Alzheimer DiseaseGenetic Predisposition to DiseaseBlack or African AmericanCaribbean PeopleEast Asian PeopleEuropean PeopleGenome-Wide Association StudyGenotypeHispanic or LatinoHumansPolymorphism, Single NucleotideSouth American People

Identifiers

PMID37198259
PMCPMC10615750

What OpenQuestion holds

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Registered trials

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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.