Evidence map›Paper›PMID 37986756›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Genetic discovery and risk prediction for type 1 diabetes in individuals without high-risk HLA-DR3/DR4 haplotypes.

Carolyn McGrail, Joshua Chiou, Ruth Elgamal, Amber M Luckett, Richard A Oram, Paola Benaglio, Kyle J Gaulton

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

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Carolyn McGrailBiomedical Sciences Graduate Program, UC San Diego, La Jolla, CA.
Joshua ChiouBiomedical Sciences Graduate Program, UC San Diego, La Jolla, CA.
Ruth ElgamalBiomedical Sciences Graduate Program, UC San Diego, La Jolla, CA.
Amber M LuckettUniversity of Exeter College of Medicine and Health, Exeter, UK.
Richard A OramUniversity of Exeter College of Medicine and Health, Exeter, UK.
Paola BenaglioDepartment of Pediatrics, UC San Diego, La Jolla, CA.
Kyle J GaultonDepartment of Pediatrics, UC San Diego, La Jolla, CA.ORCID 0000-0003-1318-7161
University of California San Diego · USUniversity of Exeter · GB

Funding

Type 1 Diabetes Genetics ConsortiumU01DK062418 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RICH, STEPHEN S. · 2002 to 2007
$59.8M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
Furthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
A Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4M
Neurodevelopmental Genomics: Trajectories of Complex PhenotypesRC2MH089983 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RAQUEL E · 2009 to 2011
$14.3M
2/2 Neurodevelopmental Genomics: Trajectories of Complex PhenotypesRC2MH089924 · NIMH · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2009 to 2011
$10.7M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059571 · NIMH · UNIVERSITY OF CHICAGO · PI GEJMAN, PABLO V. · 1999 to 2007
$8.0M
Vanderbilt Genome-Electronic Records ProjectU01HG004603 · NHGRI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2007 to 2011
$7.3M
Genetic mechanisms of type 1 diabetes risk in stress-induced pancreatic isletsR01DK122607 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE · 2019 to 2022
$4.4M
A Genome-Wide Association Study of SchizophreniaU01MH079469 · NIMH · NORTHSHORE UNIVERSITY HEALTHSYSTEM · PI GEJMAN, PABLO V. · 2007 to 2009
$4.4M
Development and Use of Network Infrastructure for High-Throughput GWA StudiesU01HG004610 · NHGRI · KAISER FOUNDATION HEALTH PLAN OF WASHINGTON · PI LARSON, ERIC B · 2007 to 2010
$4.2M
6 · The paper itself

Abstract

Over 10% of type 1 diabetes (T1D) cases do not have high-risk HLA-DR3 or DR4 haplotypes with distinct clinical features such as later onset and reduced insulin dependence. To identify genetic drivers of T1D in the absence of DR3/DR4, we performed association and fine-mapping analyses in 12,316 non-DR3/DR4 samples. Risk variants at the MHC and other loci genome-wide had heterogeneity in effects on T1D dependent on DR3/DR4, and non-DR3/DR4 T1D had evidence for a greater polygenic burden. T1D-assocated variants in non-DR3/DR4 were more enriched for loci, regulatory elements, and pathways for antigen presentation, innate immunity, and beta cells, and depleted in T cells, compared to DR3/DR4. Non-DR3/DR4 T1D cases were poorly classified based on an existing genetic risk score GRS2, and we created a new GRS which highly discriminated non-DR3/DR4 T1D from both non-diabetes and T2D. In total we identified heterogeneity in T1D genetic risk and disease mechanisms dependent on high-risk HLA haplotype and which enabled accurate classification of T1D across HLA background.

Identifiers

PMID37986756
PMCPMC10659516
OpenAlexW4388637963

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.