1. Multiple common variants for celiac disease influencing immune gene expression
- Author
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Dubois, Patrick CA, Trynka, Gosia, Franke, Lude, Hunt, Karen A, Romanos, Jihane, Curtotti, Alessandra, Zhernakova, Alexandra, Heap, Graham AR, Ádány, Róza, Aromaa, Arpo, Bardella, Maria Teresa, van den Berg, Leonard H, Bockett, Nicholas A, de la Concha, Emilio G, Dema, Bárbara, Fehrmann, Rudolf SN, Fernández-Arquero, Miguel, Fiatal, Szilvia, Grandone, Elvira, Green, Peter M, Groen, Harry JM, Gwilliam, Rhian, Houwen, Roderick HJ, Hunt, Sarah E, Kaukinen, Katri, Kelleher, Dermot, Korponay-Szabo, Ilma, Kurppa, Kalle, MacMathuna, Padraic, Mäki, Markku, Mazzilli, Maria Cristina, McCann, Owen T, Mearin, M Luisa, Mein, Charles A, Mirza, Muddassar M, Mistry, Vanisha, Mora, Barbara, Morley, Katherine I, Mulder, Chris J, Murray, Joseph A, Núñez, Concepción, Oosterom, Elvira, Ophoff, Roel A, Polanco, Isabel, Peltonen, Leena, Platteel, Mathieu, Rybak, Anna, Salomaa, Veikko, Schweizer, Joachim J, Sperandeo, Maria Pia, Tack, Greetje J, Turner, Graham, Veldink, Jan H, Verbeek, Wieke HM, Weersma, Rinse K, Wolters, Victorien M, Urcelay, Elena, Cukrowska, Bozena, Greco, Luigi, Neuhausen, Susan L, McManus, Ross, Barisani, Donatella, Deloukas, Panos, Barrett, Jeffrey C, Saavalainen, Paivi, Wijmenga, Cisca, and van Heel, David A
- Subjects
Biotechnology ,Human Genome ,Genetics ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Case-Control Studies ,Celiac Disease ,Gene Expression ,Gene Expression Profiling ,Genes ,MHC Class I ,Genome-Wide Association Study ,Humans ,Meta-Analysis as Topic ,Polymorphism ,Single Nucleotide ,Risk ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - 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.
- Published
- 2010