Evidence map›Paper›PMID 29417186›Full record

ArticleDiabetologia2018

A type 1 diabetes genetic risk score can discriminate monogenic autoimmunity with diabetes from early-onset clustering of polygenic autoimmunity with diabetes.

Matthew B Johnson, Kashyap A Patel, Elisa De Franco, Jayne A L Houghton, Timothy J McDonald, Sian Ellard, Sarah E Flanagan, Andrew T Hattersley

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In one paragraph

Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
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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

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  18. Monogenic diabetes: a gateway to precision medicine in diabetes.The Journal of clinical investigation · 2021
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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

8 authors.

Matthew B JohnsonInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK.
Kashyap A PatelInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK.
Elisa De FrancoInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK.
Jayne A L HoughtonMolecular Genetics, Royal Devon and Exeter Hospital, Exeter, UK.
Timothy J McDonaldInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK.
Sian EllardInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK.
Sarah E FlanaganInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK.
Andrew T HattersleyInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5AD, UK. A.T.Hattersley@exeter.ac.uk.

Funding

Department of Health ICA-SCL-2016-02-003Department of Health NIHR-HCS-P12-03-03Leona M. and Harry B. Helmsley Charitable Trust Breakthrough InitiativeWellcome TrustWellcome Trust 110082/Z/15/ZWellcome Trust & Royal Society 105636/Z/14/Z
6 · The paper itself

Abstract

aims/hypothesisIdentifying individuals suitable for monogenic autoimmunity testing and gene discovery studies is challenging: early-onset type 1 diabetes mellitus can cluster with additional autoimmune diseases due to shared polygenic risk and islet- and other organ-specific autoantibodies are present in both monogenic and polygenic aetiologies. We aimed to assess whether a type 1 diabetes genetic risk score (GRS) could identify monogenic autoimmune diabetes and be useful to prioritise individuals for gene discovery studies.

methodsWe studied 79 individuals with diabetes and at least one additional autoimmune disease diagnosed before the age of 5 years. We screened all participants for the seven genes known to cause monogenic autoimmunity that can include diabetes (AIRE, IL2RA, FOXP3, LRBA, STAT1, STAT3, STAT5B). We genotyped the top ten risk alleles for type 1 diabetes, including HLA and non-HLA loci, to generate a type 1 diabetes GRS.

resultsOf the 79 individuals studied, 37 (47%) had mutations in the monogenic autoimmunity genes. The type 1 diabetes GRS was lower in these individuals than in those without mutations in these genes (median 9th vs 49th centile of type 1 diabetes controls, p < 0.0001). Age of diabetes diagnosis and type 1 diabetes GRS combined to be highly discriminatory of monogenic autoimmunity (receiver operating characteristic AUC: 0.88). Most individuals without a mutation in a known gene had a high type 1 diabetes GRS, suggesting that they have polygenic clustering of type 1 diabetes and additional autoimmunity and should not be included in gene discovery studies. CONCLUSIONS/

interpretationWe have shown that the type 1 diabetes GRS can identify individuals likely to have monogenic autoimmunity, helping both diagnostic testing and novel monogenic autoimmunity gene discovery. Individuals with monogenic autoimmunity have a different clinical course to those with polygenic type 1 diabetes and can respond well to therapies targeting the underlying genetic defect.

Indexed as

AllelesAutoantibodiesAutoimmune DiseasesChild, PreschoolCluster AnalysisDiabetes Mellitus, Type 1FemaleGenetic Predisposition to DiseaseGenotypeHLA AntigensHumansInfantInfant, NewbornIslets of LangerhansMaleMutationAutoantibodiesHLA AntigensGene discoveryGenetic risk scoreMonogenic autoimmune diabetesType 1 diabetes

Identifiers

PMID29417186
PMCPMC6448971

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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.