Evidence map›Paper›PMID 37443254›Full record

ArticleNature genetics2023

Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases.

Elle M Weeks, Jacob C Ulirsch, Nathan Y Cheng, Brian L Trippe, Rebecca S Fine, Jenkai Miao, Tejal A Patwardhan, Masahiro Kanai, Joseph Nasser, Charles P Fulco 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 230 papers, 24 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
230citing papers in PubMed, 24 pooled it
84.5field-weighted citation impact, top 1% 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

230 citing papers in PubMed, 24 syntheses or guidelines pooled it, 284 citations in OpenAlex.

  1. Pooled it
  2. Genome-wide meta-analysis with 1,590,596 individuals identifies 12 novel risk loci for systemic lupus erythematosus.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Pooled it
  16. Pooled it
  17. Pooled it
  18. Pooled it
  19. Pooled it
  20. Pooled it

170 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 2 institutions in 3 countries.

Elle M Weeks *Broad Institute of MIT and Harvard, Cambridge, MA, USA. eweeks@broadinstitute.org.ORCID http://orcid.org/0000-0002-4317-4444
Jacob C Ulirsch *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7947-0827
Nathan Y ChengBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Brian L TrippeProgram in Computational & Systems Biology, MIT, Cambridge, MA, USA.
Rebecca S FineBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jenkai MiaoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Tejal A PatwardhanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Masahiro KanaiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5165-4408
Joseph NasserBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Charles P FulcoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Katherine C TashmanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Francois AguetBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9414-300X
Taibo LiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6624-9293
Jose Ordovas-MontanesBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Christopher S SmillieBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Moshe BitonBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Alex K ShalekBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Ashwin N AnanthakrishnanGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3293-3158
Rajat M GuptaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kasper LageBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kristin G ArdlieBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Joel N HirschhornBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Eric S LanderBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jesse M EngreitzBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5754-1719
Hilary K FinucaneBroad Institute of MIT and Harvard, Cambridge, MA, USA. finucane@broadinstitute.org.ORCID http://orcid.org/0000-0003-3864-9828
Broad Institute · USMassachusetts Institute of Technology · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI LYNN BRY · 1986 to 2026
$32.4M
Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
A genetic approach to identify the common mechanisms of vascular diseaseDP2HL152423 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GUPTA, RAJAT M · 2019 to 2022
$2.8M
Identifying disease-relevant cell types by integrating genetic and functional genomics dataDP5OD024582 · OD · BROAD INSTITUTE, INC. · PI FINUCANE, HILARY · 2017 to 2021
$2.2M
Systematic mapping and prediction of gene-enhancer connectionsR00HG009917 · NHGRI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2020 to 2022
$796k
Computational methods to advance from genetic association to biological insightF31HG009850 · NHGRI · HARVARD MEDICAL SCHOOL · PI FINE, REBECCA · 2017 to 2019
$85k
Systematic mapping and prediction of gene-enhancer connectionsK99HG009917 · NHGRI · BROAD INSTITUTE, INC. · PI ENGREITZ, JESSE M · 2018 to 2019
$65k
NHGRI NIH HHS F31 HG009850NHGRI NIH HHS K99 HG009917NHGRI NIH HHS R00 HG009917NHLBI NIH HHS DP2 HL152423NIDDK NIH HHS P30 DK034854NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK075787NIH HHS DP5 OD024582
6 · The paper itself

Abstract

Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene-trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene-trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox.

Indexed as

Multifactorial InheritanceQuantitative Trait LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single Nucleotide

Identifiers

PMID37443254
PMCPMC10836580
OpenAlexW4384198172

What Socratic 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 Socratic graph.