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

被引：22

作者：

Keene, K. L. ^{[1
,2
]}

Quinlan, A. R. ^{[1
,2
,3
]}

Hou, X. ^{[1
,3
]}

Hall, I. M. ^{[2
]}

Mychaleckyj, J. C. ^{[1
,3
]}

Onengut-Gumuscu, S. ^{[1
,4
]}

Concannon, P. ^{[1
,2
]}

机构：

[1] Univ Virginia, Ctr Publ Hlth Genom, UVA Sch Med, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Biochem & Mol Genet, UVA Sch Med, Charlottesville, VA 22908 USA

[3] Univ Virginia, Dept Publ Hlth Sci, UVA Sch Med, Charlottesville, VA 22908 USA

[4] Univ Virginia, Div Endocrinol & Metab, UVA Sch Med, Charlottesville, VA 22908 USA

来源：

GENES AND IMMUNITY | 2012年 / 13卷 / 01期

关键词：

ERBB3; association; gene; type; 1; diabetes; 12q13; GENOME-WIDE ASSOCIATION; METAANALYSIS; EXPRESSION; ERBB3; RISK;

D O I：

10.1038/gene.2011.56

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 similar to 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 x 10(-5)), located in exon 27 of the ERBB3 gene, and an intergenic SNP rs11171747 (P = 1.70 x 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. Genes and Immunity (2012) 13, 66-70; doi:10.1038/gene.2011.56; published online 18 August 2011

引用

页码：66 / 70

页数：5

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