Display options
Cite
Cooper JD, Howson JM, Smyth D, et al. Confirmation of novel type 1 diabetes risk loci in families. Diabetologia. 2012;55(4):996-1000doi: 10.1007/s00125-012-2450-3.
Cooper, J. D., Howson, J. M., Smyth, D., Walker, N. M., Stevens, H., Yang, J. H., She, J. X., Eisenbarth, G. S., Rewers, M., Todd, J. A., Akolkar, B., Concannon, P., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Pociot, F., Rich, S. S. (2012). Confirmation of novel type 1 diabetes risk loci in families. Diabetologia, 55(4), 996-1000. https://doi.org/10.1007/s00125-012-2450-3
Cooper, J D, et al. "Confirmation of novel type 1 diabetes risk loci in families." Diabetologia vol. 55,4 (2012): 996-1000. doi: https://doi.org/10.1007/s00125-012-2450-3
Cooper JD, Howson JM, Smyth D, Walker NM, Stevens H, Yang JH, She JX, Eisenbarth GS, Rewers M, Todd JA, Akolkar B, Concannon P, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Pociot F, Rich SS. Confirmation of novel type 1 diabetes risk loci in families. Diabetologia. 2012 Apr;55(4):996-1000. doi: 10.1007/s00125-012-2450-3. Epub 2012 Jan 26. PMID: 22278338; PMCID: PMC3296014.
Copy Download .nbib Format: NLM
Share it on

Diabetologia. 2012 Apr;55(4):996-1000. doi: 10.1007/s00125-012-2450-3. Epub 2012 Jan 26.

Confirmation of novel type 1 diabetes risk loci in families.

Diabetologia

J D Cooper, J M M Howson, D Smyth, N M Walker, H Stevens, J H M Yang, J-X She, G S Eisenbarth, M Rewers, J A Todd, B Akolkar, P Concannon, H A Erlich, C Julier, G Morahan, J Nerup, C Nierras, F Pociot, S S Rich,

Affiliations

  1. Department of Medical Genetics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. [email protected]

PMID: 22278338 PMCID: PMC3296014 DOI: 10.1007/s00125-012-2450-3

Abstract

AIMS/HYPOTHESIS: Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study.

METHODS: We genotyped the most disease-predicting single-nucleotide polymorphisms at the 18 susceptibility loci in 3,108 families and used existing genotype data for 2,319 families from the original study, providing 7,013 parent-child trios for analysis. We tested for association using the transmission disequilibrium test.

RESULTS: Seventeen of the 18 susceptibility loci reached nominal levels of significance (p < 0.05) in the expanded family collection, with 14q24.1 just falling short (p = 0.055). When we allowed for multiple testing, ten of the 17 nominally significant loci reached the required level of significance (p < 2.8 × 10(-3)). All susceptibility loci had consistent direction of effects with the original study.

CONCLUSIONS/INTERPRETATION: The results for the novel GWA study-identified loci are genuine and not due to population stratification. The next step, namely correlation of the most disease-associated genotypes with phenotypes, such as RNA and protein expression analyses for the candidate genes within or near each of the susceptibility regions, can now proceed.

References

  1. Nat Genet. 2009 Sep;41(9):1011-5 - PubMed
  2. Nat Genet. 2010 Jan;42(1):68-71 - PubMed
  3. Nat Genet. 2009 Jun;41(6):703-7 - PubMed
  4. Genome Med. 2009 Nov 24;1(11):110 - PubMed
  5. Hum Mol Genet. 2010 Jun 15;19(12):2534-8 - PubMed
  6. Nature. 2007 Jun 7;447(7145):661-78 - PubMed
  7. Genet Epidemiol. 2005 Jul;29(1):51-67 - PubMed
  8. Am J Hum Genet. 1999 Jul;65(1):229-35 - PubMed
  9. Nat Genet. 2006 Jun;38(6):617-9 - PubMed
  10. Am J Hum Genet. 2002 Jan;70(1):124-41 - PubMed

MeSH terms

Publication Types

Grant support