Multiple common variants for celiac disease influencing immune gene expression.

Patrick C A Dubois, Gosia Trynka, Lude Franke, Karen A Hunt, Jihane Romanos, Alessandra Curtotti, Alexandra Zhernakova, Graham A R Heap, Róza Adány, Arpo Aromaa, Maria Teresa Bardella, Leonard H van den Berg, Nicholas A Bockett, Emilio G de la Concha, Bárbara Dema, Rudolf S N Fehrmann, Miguel Fernández-Arquero, Szilvia Fiatal, Elvira Grandone, Peter M Green, Harry J M Groen, Rhian Gwilliam, Roderick H J Houwen, Sarah E Hunt, Katri Kaukinen, Dermot Kelleher, Ilma Korponay-Szabo, Kalle Kurppa, Padraic MacMathuna, Markku Mäki, Maria Cristina Mazzilli, Owen T McCann, M Luisa Mearin, Charles A Mein, Muddassar M Mirza, Vanisha Mistry, Barbara Mora, Katherine I Morley, Chris J Mulder, Joseph A Murray, Concepción Núñez, Elvira Oosterom, Roel A Ophoff, Isabel Polanco, Leena Peltonen, Mathieu Platteel, Anna Rybak, Veikko Salomaa, Joachim J Schweizer, Maria Pia Sperandeo, Greetje J Tack, Graham Turner, Jan H Veldink, Wieke H M Verbeek, Rinse K Weersma, Victorien M Wolters, Elena Urcelay, Bozena Cukrowska, Luigi Greco, Susan L Neuhausen, Ross McManus, Donatella Barisani, Panos Deloukas, Jeffrey C Barrett, Paivi Saavalainen, Cisca Wijmenga, David A van Heel

Nature Genetics 2010 April

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.

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