We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evidence for two independent associations with type 1 diabetes at the 12q13 locus.
- Authors
Keene, K L; Quinlan, A R; Hou, X; Hall, I M; Mychaleckyj, J C; Onengut-Gumuscu, S; Concannon, P
- Abstract
Genome-wide association studies have identified associations between type 1 diabetes and single-nucleotide polymorphisms (SNPs) at chromosome 12q13, surrounding the gene ERBB3. Our objective was to fine map this region to further localize causative variants. Re-sequencing identified more than 100 putative SNPs in an 80-kb region at 12q13. By genotyping 42 SNPs, spanning ∼214 kb, in 382 affected sibling pair type 1 diabetes families, we were able to genotype or tag 67 common SNPs (MAF0.05) identified from HapMap CEU data and CEU data from the 1000 Genomes Project, plus additional rare coding variants identified from our re-sequencing efforts. In all, 15 SNPs provided nominal evidence for association (P0.05), with type 1 diabetes. The most significant associations were observed with rs2271189 (P=4.22 × 10−5), located in exon 27 of the ERBB3 gene, and an intergenic SNP rs11171747 (P=1.70 × 10−4). Follow-up genotyping of these SNPs in 2740 multiplex type 1 diabetes families validated these findings. After analyzing variants spanning more than 200 kb, we have replicated associations from previous GWAS and provide evidence for novel associations with type 1 diabetes. The associations across this region could be entirely accounted for by two common SNPs, rs2271189 and rs11171747.
- Subjects
TYPE 1 diabetes; GENOMES; NUCLEOTIDES; GENETIC polymorphisms; CHROMOSOMES; HUMAN genetics; LOCUS (Genetics)
- Publication
Genes & Immunity, 2012, Vol 13, Issue 1, p66
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2011.56