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, Pc; Trynka, G; Francke, L; Hunt, Ka; Rpmanos, J; Curtotti, A; Zhernakova, A; Heap, Ga; Adàny, R; Aromaa, A; Bardella, Mt; Van Den Berg, Lh; Bockett, Na; De La Concha, Eg; Dema, B; Fehrmann, Rs; Fernandez Aquero, M; Fiatal, S; Grandone, E; Green, Pm; Groen, Hj; Gwilliam, R; Houwn, Rh; Hunt, Se; Kaukinen, K; Kelleher, D; Korponay Szabo, I; Kurppa, K; Mac Mathuna, P; Maki, M; Mazzilli, Mc; Mccann, Ot; Mearin, Ml; Mein, Ca; Mirza, Mm; Mistry, V; Mora, B; Morley, Ki; Mulder, Cj; Murray, Ja; Nunez, C; Oosterom, E; Ophoff, Ra; Polanco, I; Peltonen, L; Platteel, M; Rybak, A; Salomaa, V; Schweizer, Jj; Sperandeo, Mp; Tack, Gj; Turner, G; Veldink, Jh; Verbeek, Wh; Weersma, Rk; Wolters, Wm; Urcelay, E; Cukrowska, B; Greco, Luigi; Neuhausen, Sl; Mcmanus, R; Barisani, D; Deloukas, P; Barrett, Jc; Saavalainen, P; Wijmenga, C; Van Heel, Da. - 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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