Multiple common variants for celiac disease influencing immune gene expression

作者：Dubois Patrick C A; Trynka Gosia; Franke Lude; Hunt Karen A; Romanos Jihane; Curtotti Alessandra; Zhernakova Alexandra; Heap Graham A R; Adany Roza; Aromaa Arpo; Bardella Maria Teresa; van den Berg Leonard H; Bockett Nicholas A; de la Concha Emilio G; Dema Barbara; Fehrmann Rudolf S N; Fernandez Arquero Miguel; Fiatal Szilvia; Grandone Elvira; Green Peter M; Groen Harry J M; Gwilliam Rhian; Houwen Roderick H J; Hunt Sarah E; Kaukinen Katri

来源：Nature Genetics, 2010, 42(4): 295-U42.

DOI：10.1038/ng.543

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 x 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.

• 出版日期2010-4