Evidence map›Paper›PMID 37735198›Full record

ArticleNature genetics2023

Functional characterization of Alzheimer's disease genetic variants in microglia.

Xiaoyu Yang, Jia Wen, Han Yang, Ian R Jones, Xiaodong Zhu, Weifang Liu, Bingkun Li, Claire D Clelland, Wenjie Luo, Man Ying Wong and 17 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
9.0field-weighted citation impact, top 2% of its field
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

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Gut microbes · 2026
    Article
  4. Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
    Review
  16. Genetic risk in Alzheimer's disease.NPJ systems biology and applications · 2026
    Review
  17. Article
  18. Article
  19. Article
  20. Article

2 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

27 authors at 4 institutions in 1 country.

Xiaoyu YangInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jia WenDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-3273-7704
Han YangInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9150-8146
Ian R JonesInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Xiaodong ZhuHelen and Robert Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York City, NY, USA.
Weifang LiuDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2278-8946
Bingkun LiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6822-9440
Claire D ClellandDepartment of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Wenjie LuoHelen and Robert Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York City, NY, USA.ORCID http://orcid.org/0000-0003-3752-8266
Man Ying WongHelen and Robert Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York City, NY, USA.
Xingjie RenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2348-4162
Xiekui CuiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Michael SongInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3355-4806
Hongjiang LiuInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Cady ChenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4258-8899
Nicolas EngInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Mirunalini RavichandranDepartment of Anatomy, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1991-5695
Yang SunInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9344-8060
David LeeInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6539-4272
Eric Van BurenDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Min-Zhi JiangDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-5502-063X
Candace S Y ChanTetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9667-7996
Chun Jimmie YeInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6560-3783
Rushika M PereraDepartment of Anatomy, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2435-2273
Li GanHelen and Robert Appel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York City, NY, USA.ORCID http://orcid.org/0000-0003-4600-275X
Yun LiDepartment of Genetics, University of North Carolina, Chapel Hill, NC, USA. yun_li@med.unc.edu.ORCID http://orcid.org/0000-0002-9275-4189
Yin ShenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. yin.shen@ucsf.edu.ORCID http://orcid.org/0000-0001-9901-5613
University of California, San Francisco · USCornell University · USUniversity of North Carolina at Chapel Hill · USHarvard University · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
Preclinical CoreP50HD103573 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GABRIEL S DICHTER · 2020 to 2026
$9.7M
High throughput CRISPR-mediated functional validation of regulatory elementsUM1HG009402 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REN, BING, SHEN, YIN · 2017 to 2021
$8.4M
RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
Beyond GWAS: High Throughput Functional Genomics & Epigenome Editing to Elucidate the Effects of Genetic Associations for SchizophreniaR01MH125236 · NIMH · DUKE UNIVERSITY · PI CRAWFORD, GREGORY E, GERSBACH, CHARLES A. · 2021 to 2025
$8.1M
Elucidate the roles of Alzheimer's disease risk genes and variants in gene expression and AD-related phenotypesRF1AG079557 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAN, LI, SHEN, YIN · 2022 to 2025
$6.1M
Study of Selective Cell and System Vulnerability in Alzheimer's DiseaseR01AG079291 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Li Gan, Yun Li · 2023 to 2026
$5.4M
Polygenic risk scores for cardiometabolic disorders: the role of blood cells immune response and evolutionary adaptationU01HG011720 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Yun Li, ALEXANDER P REINER · 2021 to 2026
$5.4M
A Trans-Nordic Study of Extreme Major DepressionR01MH123724 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PATRICK F SULLIVAN, Lu Yi · 2020 to 2026
$4.7M
Functional characterization of Alzheimer's disease associated genetic variantsR01AG057497 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAN, LI, SHEN, YIN · 2017 to 2021
$4.2M
Maladaptive antiviral pathways in Alzheimer's diseaseR01AG072758 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2021 to 2025
$4.1M
Tau acetylation in Alzheimer's diseaseR01AG054214 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI GAN, LI · 2017 to 2021
$3.3M
NEI NIH HHS R01 EY027789NHGRI NIH HHS U01 HG011720NHGRI NIH HHS UM1 HG009402NIAMS NIH HHS P30 AR070155NIA NIH HHS R01 AG054214NIA NIH HHS R01 AG057497NIA NIH HHS R01 AG072758NIA NIH HHS R01 AG079291NIA NIH HHS R56 AG079291NIA NIH HHS RF1 AG079557NICHD NIH HHS P50 HD103573NIDDK NIH HHS P30 DK063720NIGMS NIH HHS T32 GM144291NIH HHS S10 OD021822NIH HHS S10 OD028511NIMH NIH HHS R01 MH123724NIMH NIH HHS R01 MH125236
6 · The paper itself

Abstract

Candidate cis-regulatory elements (cCREs) in microglia demonstrate the most substantial enrichment for Alzheimer's disease (AD) heritability compared to other brain cell types. However, whether and how these genome-wide association studies (GWAS) variants contribute to AD remain elusive. Here we prioritize 308 previously unreported AD risk variants at 181 cCREs by integrating genetic information with microglia-specific 3D epigenome annotation. We further establish the link between functional variants and target genes by single-cell CRISPRi screening in microglia. In addition, we show that AD variants exhibit allelic imbalance on target gene expression. In particular, rs7922621 is the effective variant in controlling TSPAN14 expression among other nominated variants in the same cCRE and exerts multiple physiological effects including reduced cell surface ADAM10 and altered soluble TREM2 (sTREM2) shedding. Our work represents a systematic approach to prioritize and characterize AD-associated variants and provides a roadmap for advancing genetic association to experimentally validated cell-type-specific phenotypes and mechanisms.

Indexed as

Alzheimer DiseaseCell MembraneGenome-Wide Association StudyHumansMicrogliaPhenotype

Identifiers

PMID37735198
PMCPMC10939305
OpenAlexW4386923851

What OpenQuestion holds

Textmetadata
LicenceTDM
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.