Evidence for two independent associations with type 1 diabetes at the 12q13 locus

K. L. Keene, A. R. Quinlan, X. Hou, I. M. Hall, J. C. Mychaleckyj, S. Onengut-Gumuscu, P. Concannon

Research output: Contribution to journalArticle

16 Scopus citations

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 (MAF>0.05) 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 (P≤0.05), 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.

Original languageEnglish
Pages (from-to)66-70
Number of pages5
JournalGenes and Immunity
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • 12q13
  • ERBB3
  • association
  • gene
  • type 1 diabetes

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    Keene, K. L., Quinlan, A. R., Hou, X., Hall, I. M., Mychaleckyj, J. C., Onengut-Gumuscu, S., & Concannon, P. (2012). Evidence for two independent associations with type 1 diabetes at the 12q13 locus. Genes and Immunity, 13(1), 66-70. https://doi.org/10.1038/gene.2011.56