Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Overview of the Rapid Response data

Abstract

The Type I Diabetes Genetics Consortium (T1DGC) Rapid Response Workshop was established to evaluate published candidate gene associations in a large collection of affected sib-pair (ASP) families. We report on our quality control (QC) and preliminary family-based association analyses. A random sample of blind duplicates was analyzed for QC. Quality checks, including examination of plate-panel yield, marker yield, Hardy–Weinberg equilibrium, mismatch error rate, Mendelian error rate, and allele distribution across plates, were performed. Genotypes from 2324 families within nine cohorts were obtained from a panel of 21 candidate genes, including 384 single-nucleotide polymorphisms on two genotyping platforms performed at the Broad Institute Center for Genotyping and Analysis (Cambridge, MA, USA). The T1DGC Rapid Response project, following rigorous QC procedures, resulted in a 2297 family, 9688 genotyped individual database on a single-candidate gene panel. The available data include 9005 individuals with genotype data from both platforms and 683 individuals genotyped (276 in Illumina; 407 in Sequenom) on only one platform.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 1994; 371: 130–136.

    Article  CAS  Google Scholar 

  2. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506–511.

    Article  CAS  Google Scholar 

  3. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004; 36: 337–338.

    Article  CAS  Google Scholar 

  4. Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D et al. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat Genet 2004; 36: 837–841.

    Article  CAS  Google Scholar 

  5. Noble JA, White AM, Lazzeroni LC, Valdes AM, Mirel DB, Reynolds R et al. A polymorphism in the TCF7 gene, C883A, is associated with type 1 diabetes. Diabetes 2003; 52: 1579–1582.

    Article  CAS  Google Scholar 

  6. Cooper JD, Smyth DJ, Bailey R, Payne F, Downes K, Godfrey LM et al. The candidate genes TAF5 L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes. BMC Med Genet 2007; 8: 71–85.

    Article  Google Scholar 

  7. Julier C, Akolkar B, Concannon P, Morahan G, Nierras C, Pugliese A and the Type I Diabetes Genetics Consortium. The Type I Diabetes Genetics Consortium ‘Rapid Response’ family-based candidate gene study: strategy, genes selection, and main outcome. Genes Immun 2009; 10 (Suppl 1): S121–S127.

    Article  CAS  Google Scholar 

  8. Concannon P, Erlich HA, Julier C, Morahan G, Nerup J, Pociot F et al. Type 1 diabetes: evidence for susceptibility loci from four genome-wide linkage scans in 1,435 multiplex families. Diabetes 2005; 54: 2995–3001.

    Article  CAS  Google Scholar 

  9. Concannon P, Chen WM, Julier C, Morahan G, Akolkar B, Erlich HA et al. Genome-wide scan for linkage to type 1 diabetes in 2,496 multiplex families from the Type 1 Diabetes Genetics Consortium. Diabetes 2009; 58: 1018–1022.

    Article  CAS  Google Scholar 

  10. Fine Mapping of the MHC Region for Type 1 Diabetes Genes: Proceedings of the Type 1 Diabetes Genetics Consortium MHC Fine Mapping Workshop, Washington, DC, 27–28 August 2007. Diabetes Obes Metab 2009; 11 (Suppl 1): pp 1–109.

  11. de Bakker PIW, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D . Efficiency and power in genetic association studies. Nat Genet 2005; 37: 1217–1223.

    Article  CAS  Google Scholar 

  12. O’Connell JR, Weeks DE . PedCheck: a program for identifying marker typing incompatibilities in linkage analysis. Am J Hum Genet 1998; 63: 259–266.

    Article  Google Scholar 

  13. McPeek MS, Sun L . Statistical tests for detection of misspecified relationships by use of genome-screen data. Am J Hum Genet 2000; 66: 1076–1094.

    Article  CAS  Google Scholar 

  14. Abecasis GR, Cherny SS, Cookson WO, Cardon LR . GRR: graphical representation of relationship errors. Bioinformatics 2001; 17: 742–743.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research uses resources provided by the Type I Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD), and the Juvenile Diabetes Research Foundation International (JDRF), and supported by U01 DK062418. We appreciate the technical assistance of the entire CGA Illumina team as led by Jamie Moore, and of the Sequenom team (led by LZ), with particular thanks to Rob Borkowski and Cherylyn Smith. Genotyping was performed at the Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to W M Brown.

Appendix

Appendix

Table A1

Table a1 Appendix A: Rapid Response reference SNP list

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, W., Pierce, J., Hilner, J. et al. Overview of the Rapid Response data. Genes Immun 10 (Suppl 1), S5–S15 (2009). https://doi.org/10.1038/gene.2009.85

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2009.85

Keywords

This article is cited by

Search

Quick links