Multiple common variants for celiac disease influencing immune gene expression

Dubois, P.C.A.; Trynka, G.; Franke, L.; Hunt, K.A.; Romanos, J.; Curtotti, A.; ... ; Heel, D.A. van (2010)

Article / Letter to editor

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.

• genome-wide association rheumatoid-arthritis susceptibility loci positive selection risk variants population alleles thymus heterodimer thymocytes

• All authors: Dubois, P.C.A.; Trynka, G.; Franke, L.; Hunt, K.A.; Romanos, J.; Curtotti, A.; Zhernakova, A.; Heap, G.A.R.; Adany, R.; Aromaa, A.; Bardella, M.T.; Berg, L.H. van den; Bockett, N.A.; Concha, E.G. de la; Dema, B.; Fehrmann, R.S.N.; Fernandez-Arquero, M.; Fiatal, S.; Grandone, E.; Green, P.M.; Groen, H.J.M.; Gwilliam, R.; Houwen, R.H.J.; Hunt, S.E.; Kaukinen, K.; Kelleher, D.; Korponay-Szabo, I.; Kurppa, K.; MacMathuna, P.; Maki, M.; Mazzilli, M.C.; McCann, O.T.; Mearin, M.L.; Mein, C.A.; Mirza, M.M.; Mistry, V.; Mora, B.; Morley, K.I.; Mulder, C.J.; Murray, J.A.; Nunez, C.; Oosterom, E.; Ophoff, R.A.; Polanco, I.; Peltonen, L.; Platteel, M.; Rybak, A.; Salomaa, V.; Schweizer, J.J.; Sperandeo, M.P.; Tack, G.J.; Turner, G.; Veldink, J.H.; Verbeek, W.H.M.; Weersma, R.K.; Wolters, V.M.; Urcelay, E.; Cukrowska, B.; Greco, L.; Neuhausen, S.L.; McManus, R.; Barisani, D.; Deloukas, P.; Barrett, J.C.; Saavalainen, P.; Wijmenga, C.; Heel, D.A. van
• Date: 2010-04-30
• Journal: Nature Genetics
• Volume: 42
• Issue: 4
• Pages: 295
• DOI: doi:10.1038/ng.543