{
  "abstract": "Introduction Type 1 diabetes is an autoimmune disease with a strong genetic basis. The aim of this study was to identify additional single-nucleotide polymorphisms (SNPs) for type 1 diabetes age at diagnosis and to replicate previously identified loci.Research design and methods Meta genome-wide association studies of age at diagnosis from eight cohorts (n=5910 in total) were performed in three models. Model 1 was age at diagnosis with no covariates. Model 2 was age at diagnosis adjusted for DR3/DR4 genotype categories. Model 3 was similar to model 2, including the most significant SNP from model 2 (coded additively). Models 1 and 2 were also performed for major histocompatibility complex (MHC) imputed data. In addition, we tested previously identified loci for age at diagnosis and type 1 diabetes risk for association with age at diagnosis in model 1.Results In model 1, we identified a genome-wide significant locus (rs2856721, p=3.3×10 −11) in the MHC region whose effect was attenuated in model 2 (p=0.03). In model 2, we identified another locus in the MHC region, rs76730244, p=4.9×10−9, which was associated with age at diagnosis adjusted for DR3/DR4 genotypes. Model 3 and analysis of the MHC region did not reveal novel loci. Among 14 previously identified SNPs for age at diagnosis, 6 were confirmed; in addition, 11 out of 78 non-HLA loci for type 1 diabetes risk were associated with age at diagnosis.Conclusions We identified rs76730244 in the MHC region for age at diagnosis of type 1 diabetes, which was independent of the HLA-DR3/DR4 genotype categories. We also confirmed 6 previously identified SNPs and showed that 11 non-HLA loci for type 1 diabetes risk are associated with age at diagnosis.",
  "authors": [
    {
      "affiliations": [
        "University Medical Center Groningen, Endocrinology, University of Groningen, Groningen, Groningen, The Netherlands"
      ],
      "name": "Charlotte E Vollenbrock"
    },
    {
      "affiliations": [
        "Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Delnaz Roshandel"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA"
      ],
      "name": "Kristine E Lee"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA"
      ],
      "name": "Barbara E Klein"
    },
    {
      "affiliations": [
        "Diabeter, Center for Type 1 Diabetes Care and Research, Rotterdam, The Netherlands"
      ],
      "name": "Dick Mul"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, Endocrinology, University of Groningen, Groningen, Groningen, The Netherlands"
      ],
      "name": "Melanie M van der Klauw"
    },
    {
      "affiliations": [
        "Internal Medicine, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands"
      ],
      "name": "Cornelis J Tack"
    },
    {
      "affiliations": [
        "BDC Clinical EPI Research, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "Marian Rewers"
    },
    {
      "affiliations": [
        "BDC Clinical EPI Research, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "Janet K Snell-Bergeon"
    },
    {
      "affiliations": [
        "Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Tina Costacou"
    },
    {
      "affiliations": [
        "Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"
      ],
      "name": "Rachel G Miller"
    },
    {
      "affiliations": [
        "Division of diabetes, University of Minnesota Department of Medicine, Minneapolis, Minnesota, USA"
      ],
      "name": "Maria Luiza Caramori"
    },
    {
      "affiliations": [
        "Division of diabetes, University of Minnesota Department of Medicine, Minneapolis, Minnesota, USA"
      ],
      "name": "Mike Mauer"
    },
    {
      "affiliations": [
        "Diabeter, Center for Type 1 Diabetes Care and Research, Rotterdam, The Netherlands"
      ],
      "name": "Henk-Jan Aanstoot"
    },
    {
      "affiliations": [
        "University Medical Center Groningen, Endocrinology, University of Groningen, Groningen, Groningen, The Netherlands"
      ],
      "name": "Bruce H R Wolffenbuttel"
    },
    {
      "affiliations": [
        "Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada",
        "Divisions of Biostatistics and Epidemiology, University of Toronto Dalla Lana School of Public Health, Toronto, Ontario, Canada"
      ],
      "name": "Andrew D Paterson"
    },
    {
      "affiliations": [],
      "name": "DCCT/EDIC Research Group"
    }
  ],
  "title": "Association of genetic variation with age at diagnosis in type 1 diabetes",
  "uid": "fe706290-cb2c-5d46-bac3-121dba9e2e6a"
}