Evidence map›Paper›PMID 28438156›Full record

ArticleBMC medicine2017

Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes.

Rajashree Mishra, Alessandra Chesi, Diana L Cousminer, Mohammad I Hawa, Jonathan P Bradfield, Kenyaita M Hodge, Vanessa C Guy, Hakon Hakonarson, Bone Mineral Density in Childhood Study, Didac Mauricio and 7 more

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

Article in BMC medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
11.0field-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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
  2. Observational
  3. Review
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  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Adult-onset autoimmune diabetes.Nature reviews. Disease primers · 2022
    Review
  13. Review
  14. Review
  15. Latent autoimmune diabetes in adults in China.Frontiers in immunology · 2022
    Review
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  17. Article
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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

17 authors at 5 institutions in 6 countries.

Rajashree MishraDivision of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Alessandra ChesiDivision of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Diana L CousminerDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mohammad I HawaDepartment of Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Jonathan P BradfieldCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Kenyaita M HodgeDivision of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Vanessa C GuyDivision of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Hakon HakonarsonDivision of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Bone Mineral Density in Childhood Study
Didac MauricioHospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Nanette C SchlootGerman Diabetes Center, Düsseldorf, Germany.
Knud B YderstrædeOdense University Hospital, Odense, Denmark.
Benjamin F VoightDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stanley SchwartzMain Line Health System, Wynnewood, PA, USA.
Bernhard O BoehmDepartment of Internal Medicine I, Ulm University Medical Centre, Ulm, Germany.
Richard David LeslieDepartment of Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. r.d.g.leslie@qmul.ac.uk.
Struan F A GrantDivision of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. grants@chop.edu.
Children's Hospital of Philadelphia · USQueen Mary University of London · GBMain Line Health · USOdense University Hospital · DKDeutsches Diabetes-Zentrum e.V. · DE

Funding

Training Grant in Pediatric Endocrinology, Diabetes and MetabolismT32DK065522 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SHARON E. OBERFIELD · 2005 to 2026
$4.6M
Genome Wide Association Study of Latent Autoimmune Diabetes in AdultsR01DK085212 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A · 2011 to 2016
$3.4M
Algorithms to identify non-coding mutational burden and disease-relevant pathwaysR01DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2014 to 2018
$2.9M
NIDDK NIH HHS R01 DK085212NIDDK NIH HHS R01 DK101478NIDDK NIH HHS T32 DK065522Wellcome Trust
6 · The paper itself

Abstract

backgroundIn adulthood, autoimmune diabetes can present as non-insulin-requiring diabetes, termed as 'latent autoimmune diabetes in adults' (LADA). In this study, we investigated established type 1 diabetes (T1D) and type 2 diabetes (T2D) genetic loci in a large cohort of LADA cases to assess where LADA is situated relative to these two well-characterized, classic forms of diabetes.

methodsWe tested the association of T1D and T2D GWAS-implicated loci in 978 LADA cases and 1057 non-diabetic controls of European ancestry using a linear mixed model. We then compared the associations of T1D and T2D loci between LADA and T1D and T2D cases, respectively. We quantified the difference in genetic risk between each given disease at each locus, and also calculated genetic risk scores to quantify how genetic liability to T1D and T2D distinguished LADA cases from controls.

resultsOverall, our results showed that LADA is genetically more similar to T1D, with the exception of an association at the T2D HNF1A locus. Several T1D loci were associated with LADA, including the major histocompatibility complex region, as well as at PTPN22, SH2B3, and INS. Contrary to previous studies, the key T2D risk allele at TCF7L2 (rs7903146-T) had a significantly lower frequency in LADA cases, suggesting that this locus does not play a role in LADA etiology. When constrained on antibody status, the similarity between LADA and T1D became more apparent; however, the HNF1A and TCF7L2 observations persisted.

conclusionLADA is genetically closer to T1D than T2D, although the genetic load of T1D risk alleles is less than childhood-onset T1D, particularly at the major histocompatibility complex region, potentially accounting for the later disease onset. Our results show that the genetic spectrum of T1D extends into adult-onset diabetes, where it can clinically masquerade as T2D. Furthermore, T2D genetic risk plays a small role in LADA, with a degree of evidence for the HNF1A locus, highlighting the potential for genetic risk scores to contribute towards defining diabetes subtypes.

Indexed as

AdultAgedAllelesDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2HumansMiddle AgedProtein Tyrosine Phosphatase, Non-Receptor Type 22Protein Tyrosine Phosphatase, Non-Receptor Type 22PTPN22 protein, humanGenetic risk scoresLatent autoimmune diabetes in adults

Identifiers

PMID28438156
PMCPMC5404312
OpenAlexW2606216134

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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 OpenQuestion graph.