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.
Multiple common variants for celiac disease influencing immnune gene expression / Dubois, P.c., Trynka, G., Francke, L., Hunt, K.a., Rpmanos, J., Curtotti, A., Zhernakova, A., Heap, G.a., Adàny, R., Aromaa, A., Bardella, M.t., Van Den Berg, L.h., Bockett, N.a., De La Concha, E.g., Dema, B., Fehrmann, R.s., Fernandez Aquero, M., Fiatal, S., Grandone, E., Green, P.m., et al.. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 42:(2010), pp. 295-302.
Multiple common variants for celiac disease influencing immnune gene expression
GRECO, LUIGI;
2010
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 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.| File | Dimensione | Formato | |
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