Evidence map›Paper›PMID 37749083›Full record

ArticleScientific data2023

Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity.

Clare E West, Mohd Karim, Maria J Falaguera, Leo Speidel, Charlotte J Green, Lisa Logie, Jeremy Schwartzentruber, David Ochoa, Janet M Lord, Michael A J Ferguson and 6 more

Open access · goldAbstract read
In one paragraph

Article in Scientific data, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 18% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. 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

16 authors at 8 institutions in 2 countries.

Clare E WestCentre for Medicines Discovery, University of Oxford, Oxford, UK. clarewestc@gmail.com.ORCID http://orcid.org/0000-0001-5677-8215
Mohd KarimOpen Targets, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0003-2960-6017
Maria J FalagueraOpen Targets, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0002-6635-4982
Leo SpeidelFrancis Crick Institute, London, UK.
Charlotte J GreenDrug Discovery Unit, University of Dundee, Dundee, UK.
Lisa LogieDrug Discovery Unit, University of Dundee, Dundee, UK.
Jeremy SchwartzentruberEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0002-6183-2092
David OchoaOpen Targets, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0003-1857-278X
Janet M LordMRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0003-1030-6786
Michael A J FergusonDrug Discovery Unit, University of Dundee, Dundee, UK.ORCID http://orcid.org/0000-0003-1321-8714
Chas BountraCentre for Medicines Discovery, University of Oxford, Oxford, UK.
Graeme F WilkinsonMedicines Discovery Catapult, 35 Mereside Alderley Park, Macclesfield, Cheshire, UK.ORCID http://orcid.org/0000-0001-5855-2025
Beverley VaughanCentre for Medicines Discovery, University of Oxford, Oxford, UK.
Andrew R LeachOpen Targets, Wellcome Genome Campus, Hinxton, UK.ORCID http://orcid.org/0000-0001-8178-0253
Ian DunhamOpen Targets, Wellcome Genome Campus, Hinxton, UK.
Brian D MarsdenCentre for Medicines Discovery, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1937-4091
European Bioinformatics Institute · GBUniversity of Dundee · GBUniversity of Oxford · GBDiscovery Centre · CAMedicines Discovery Catapult · GBThe Francis Crick Institute · GBUniversity Hospitals Birmingham NHS Foundation Trust · GBWellcome Sanger Institute · GB

Funding

Medical Research Council MR/K00414X/1Wellcome TrustWellcome Trust 206194
6 · The paper itself

Abstract

Advancing age is the greatest risk factor for developing multiple age-related diseases. Therapeutic approaches targeting the underlying pathways of ageing, rather than individual diseases, may be an effective way to treat and prevent age-related morbidity while reducing the burden of polypharmacy. We harness the Open Targets Genetics Portal to perform a systematic analysis of nearly 1,400 genome-wide association studies (GWAS) mapped to 34 age-related diseases and traits, identifying genetic signals that are shared between two or more of these traits. Using locus-to-gene (L2G) mapping, we identify 995 targets with shared genetic links to age-related diseases and traits, which are enriched in mechanisms of ageing and include known ageing and longevity-related genes. Of these 995 genes, 128 are the target of an approved or investigational drug, 526 have experimental evidence of binding pockets or are predicted to be tractable, and 341 have no existing tractability evidence, representing underexplored genes which may reveal novel biological insights and therapeutic opportunities. We present these candidate targets for exploration and prioritisation in a web application.

Indexed as

AgingGenome-Wide Association StudyMultimorbidityHumansLongevityPhenotype

Identifiers

PMID37749083
PMCPMC10520009
OpenAlexW4387014311

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.