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Confirmation of novel type 1 diabetes risk loci in families.
- Source :
- Diabetologia; Apr2012, Vol. 55 Issue 4, p996-1000, 5p, 1 Chart
- Publication Year :
- 2012
-
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). 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0012186X
- Volume :
- 55
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 72456624
- Full Text :
- https://doi.org/10.1007/s00125-012-2450-3