Multiple common variants for celiac disease influencing immune gene expression

PCA Dubois, G Trynka, L Franke, KA Hunt… - Nature …, 2010 - nature.com
PCA Dubois, G Trynka, L Franke, KA Hunt, J Romanos, A Curtotti, A Zhernakova, GAR Heap
Nature genetics, 2010nature.com
We performed a second-generation genome-wide association study of 4,533 individuals
with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs
with P GWAS< 10− 4 and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684
controls. Variants from 13 new regions reached genome-wide significance (P combined< 5×
10− 8); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-
CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key …
Abstract
We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with PGWAS < 10−4 and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (Pcombined < 5 × 10−8); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression.
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