We tested 310,605 single-nucleotide polymorphisms for association in 778 celiac disease cases and 1422 controls. Outside the HLA, the most significant finding (rs13119723, P=2.0 × 10−7, empirical genome-wide significance P=0.045) was in the KIAA1109/Tenr/IL2/IL21 linkage disequilibrium block. Association was independently confirmed in two further collections (strongest at rs6822844, 24kB 5' of IL21, meta-analysis P=1.3 × 10−14, OR 0.63), suggesting genetic variation in this region predisposes to celiac disease. ; PUBLISHED ; We acknowledge funding from Coeliac UK; the Coeliac Disease Consortium (an innovative cluster approved by the Netherlands Genomics Initiative and partly funded by the Dutch Government, grant BSIK03009); the Netherlands Genomics Initiative (grant 050-72-425); the Netherlands Organization for Scientific Research (grant 901-04-219); the Science Foundation Ireland and the Wellcome Trust (GR068094MA Clinician Scientist Fellowship to D.A.vH; New Blood Fellowship to R.M.; support for the work of R.McG and P.D.). The authors acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02.