Type 1 Diabetes Genetics Consortium: A multi-ancestry, genome-wide association study of type 1 diabetes
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PROVIDER: PRJNA1072819 | ENA |
REPOSITORIES: ENA
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Project description:Type 1 Diabetes Genetics Consortium: A multi-ancestry, genome-wide association study of type 1 diabetes
| PRJNA1072818 | ENA
Project description:Type 1 Diabetes Genetics Consortium (T1DGC) CNV Study
| PRJNA284781 | ENA
Project description:Type 1 Diabetes Genetics Consortium (T1DGC) ImmunoChip Study
| PRJNA285005 | ENA
Project description:Type 1 Diabetes Genetics Consortium (T1DGC): Multi-Ethnic ImmunoChip Study
| PRJNA738975 | ENA
Project description:Type 1 Diabetes Genetics Consortium (T1DGC): Multi-Ethnic ImmunoChip Study
| PRJNA738974 | ENA
Project description:The Type 1 Diabetes Genetics Consortium is a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. Its aim is to develop resources for the scientific community to identify genes influencing an individuals risk for developing Type 1 (juvenile onset) Diabetes (T1D).
| EGAO00000000012 | EGA
Project description:<p>Cases with Type 1 Diabetes (T1D) in the UK, were part of the Wellcome Trust Case Control Consortium (WTCCC) - <a href="http://www.wtccc.org.uk" target="_blank">http://www.wtccc.org.uk</a> - that first reported in 2007:</p> <p>Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661-678. [PubMed: <a href="http://www.ncbi.nlm.nih.gov/pubmed/17554300" target="_blank">17554300</a>]</p> <p>In this genome-wide association study (GWAS), funded by the NIH and JDRF, and sponsored by the Type 1 Diabetes Genetics Consortium (T1DGC), we were able to extend the case and control groups used in the WTCCC, with the intention of performing a well-powered meta-analysis.</p> <p>The study is written up as:</p> <p>Barrett, J.C., Clayton, D.G., Concannon, P., Akolkar, B., Cooper, J.D., Erlich, H.A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Plagnol, V., Pociot, F., Schuilenburg, H., Smyth, D.J., Stevens, H., Todd, J.A., Walker, N.M., Rich, S.S. and The Type 1 Diabetes Genetics Consortium Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19430480" target="_blank">19430480</a>.</p> <p>Resources - data:</p> <p>* Case data from this study is deposited here (i.e. in dbGaP)</p> <p>* Control data from this experiment - with subjects from the 1958 British Birth Cohort - is deposited with the European Genotype Archive (EGA):</p> <p><a href="http://www.ebi.ac.uk/ega/" target="_blank">http://www.ebi.ac.uk/ega/</a></p> <p>from where the WTCCC data is also available.</p> <p>* A complete description of how to request all components of the meta-analysis is available at:</p> <p><a href="http://www.t1dbase.org/page/PosterView/display/poster_id/324" target="_blank">http://www.t1dbase.org/page/PosterView/display/poster_id/324</a></p> <p>* Additional genetic data on the same case subjects, including some HLA types, are available from the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory (JDRF/WT-DIL):</p> <p><a href="http://www-gene.cimr.cam.ac.uk/todd/" target="_blank">http://www-gene.cimr.cam.ac.uk/todd/</a></p> <p>Resources - samples:</p> <p>Case and control DNA samples are also available:</p> <p>* Case DNA samples are available from the JDRF/WT-DIL, as above, and will be available from the NIDDK Genetics Repository at Rutgers:</p> <p><a href="https://www.niddkrepository.org" target="_blank">https://www.niddkrepository.org</a></p> <p>* Control DNA samples are available from the 1958 British Birth Cohort (aka National Child Development Study):</p> <p><a href="http://www.cls.ioe.ac.uk/studies.asp?section=000100020003" target="_blank">http://www.cls.ioe.ac.uk/studies.asp?section=000100020003</a></p> <p>Use restrictions:</p> <p>There are access limitations to both data and samples, in order to keep their use in line with subjects' consent.</p>
| phs000180.v2.p2 | EGA
Project description:In recent years the pace of discovery of genetic associations with type I diabetes (T1D) has accelerated, with the total number of confirmed loci, including the major histocompatibility complex (MHC) region, reaching 43. However, much of the deciphering of the associations at these, and the established T1D loci, has yet to be performed in sufficient numbers of samples or with sufficient markers. Here, 257 single-nucleotide polymorphisms (SNPs) have been genotyped in 19 candidate genes (INS, PTPN22, IL2RA, CTLA4, IFIH1, SUMO4, VDR, PAX4, OAS1, IRS1, IL4, IL4R, IL13, IL12B, CEACAM21, CAPSL, Q7Z4c4(5Q), FOXP3, EFHB) in 2300 affected sib-pair families and tested for association with T1D as part of the Type I Diabetes Genetics Consortium's candidate gene study. The study had approximately 80% power at alpha=0.002 and a minor allele frequency of 0.2 to detect an effect with a relative risk (RR) of 1.20, which drops to just 40% power for a RR of 1.15. At the INS gene, rs689 (-23 HphI) was the most associated SNP (P=3.8 x 10(-31)), with the estimated RR=0.57 (95% confidence interval, 0.52-0.63). In addition, rs689 was associated with age-at-diagnosis of T1D (P=0.001), with homozygosity for the T1D protective T allele, delaying the onset of T1D by approximately 2 years in these families. At PTPN22, rs2476601 (R620W), in agreement with previous reports, was the most significantly associated SNP (P=6.9 x 10(-17)), with RR=1.55 (1.40-1.72). Evidence for association with T1D was observed for the IFIH1 SNP, rs1990760 (P=7.0 x 10(-4)), with RR=0.88 (0.82-0.95) and the CTLA4 SNP rs1427676 (P=0.0005), with RR=1.14 (1.06-1.23). In contrast, no convincing evidence of association was obtained for SUMO4, VDR, PAX4, OAS1, IRS1, IL4, IL4R, IL13, IL12B, CEACAM21 or CAPSL gene regions (http://www.T1DBase.org).
| S-EPMC2810493 | biostudies-literature
Project description:BackgroundAutoimmune thyroiditis occurs in 10-25% of patients with type 1 diabetes (T1D). Most of these patients are also positive for thyroid peroxidase (TPO) antibodies. Thyroid dysfunction complicates T1D metabolic control and is a component of the autoimmune polyglandular syndrome (APS, type 2 or 3). Previous studies of isolated T1D and of T1D combined with other autoimmune disorders showed genetic susceptibility for alleles in HLA-DQB1 and -DRB1 and also CTLA4 and PTPN22.Research design and methodsWe analyzed the Type 1 Diabetes Genetics Consortium Autoantibody Workshop data by differentiating those T1D probands with and without TPO antibodies or thyroid disease with respect to polymorphisms in HLA, CTLA4, INS, PTPN22, and VDR, taking into account the ethnic origin. Genotype and clinical/immunogenic phenotype data were analyzed by gene counting methods and logistic regression analysis.ResultsThe presence of TPO antibodies (25.2%) and thyroid disease (8.4%) was associated with older age, female sex, and presence of other autoantibodies (GAD65, ATPase, 21-OH) (all P<0.001). The highest prevalence was in patients of Hispanic ancestry (31%) and the lowest in those of African ancestry (8%). In T1D non-Hispanic whites, HLA-DRB1*0101 is significantly (P<0.0001) less frequent in TPO-positive than in TPO-negative individuals, whereas HLA-DRB1*0404, -DQB1*0301, and -DPB1*0201 are significantly (P<0.0001) more frequent. Subjects with a high titer of TPO autoantibodies and with thyroid disease were associated with female sex and older age and negatively associated with DRB1*0401-DQB1*0302 (P<0.0001). No significant differences were observed for an association of TPO positivity or thyroid disease with single nucleotide polymorphisms in the INS, CTLA4, or VDR loci, with nominal significance (P=0.01) for PTPN22 R620W variant.ConclusionsThyroid autoimmunity is highly prevalent in T1D patients of non-Hispanic white, Asian, or Hispanic origin. The strongest disease risk is conferred by female sex and older age. This risk is modulated by HLA-DRB1 and HLA-DPB1 loci. The immunogenetic profile for T1D with thyroid autoimmunity may identify distinct pathways regulating polyglandular autoimmunity and disease.
| S-EPMC4582911 | biostudies-literature