Received: 4 April 2018 Revised: 2 October 2018 Accepted: 15 October 2018 DOI: 10.1111/ahg.12293 ORIGINAL ARTICLE Expression patterns common and unique to ulcerative colitis and celiac disease Luz María Medrano 1 ∗ Virginia Pascual 1 ∗ Andrés Bodas 2 Natalia López-Palacios 3 Isabel Salazar 4 Laura Espino-Paisán 5 Beatriz González-Pérez 6 Elena Urcelay 5 Juan Luis Mendoza 3 Concepción Núñez 5 1 Servicio de Inmunología Clínica, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain 2 Servicio de Pediatría, Instituto de Investi- gación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain 3 Servicio de Aparato Digestivo, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain 4 Departamento de Producción Animal, Facul- tad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain 5 Laboratorio de Investigación en Genética de Enfermedades Complejas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain 6 Departamento de Estadística e Investigación Operativa I, Facultad de Matemáticas, Uni- versidad Complutense de Madrid, Madrid, Spain Correspondence Laura Espino-Paisán, Laboratorio de Genética de Enfermedades Complejas, Hospital Clínico San Carlos, C/ Martín Lagos s/n, 28040 Madrid, Spain. Email: lauraep80@gmail.com ∗ These authors contributed equally to this work. Abstract Autoimmune diseases like celiac disease (CeD) and ulcerative colitis (UC) show a common genetic background defined by the existence of shared susceptibility loci. We aimed to go deeper into this common genetic background through performing a cross-disease study based on gene expression. We measured the expression of 21 genes located in 13 CeD-UC susceptibility regions, and 10 genes in five CeD risk regions. Determinations were carried out in colon/rectum samples from 13 UC patients (inflamed and uninflamed tissue) and four colon samples from controls. Duodenal samples from 19 CeD patients and 12 controls were used for compar- isons. Differences were analyzed using the Bayesian method. The shared chromo- somal regions containing TNFAIP3, PTPN2, ICOSLG, C1orf106, and IL21 showed similar results in both diseases. FASLG, PLEK, CCR4, and TAGAP, all located in CeD risk loci, were up-regulated in both CeD and UC patients. Finally, ZFP36L1, ZMIZ1, PUS10, UBE2L3, and BACH2 showed opposite results in CeD and UC. A high complexity underlies autoimmune common susceptibility loci, as the expression pattern of the studied genes does not always correlate with the one expected attending to the apparent genetic background. Differentially expressed genes such as ZFP36L1, ZMIZ1, PUS10, and BACH2 deserve further research in autoimmune diseases. KEYWORDS association signals, autoimmune diseases, candidate genes, disease susceptibility, gene expression 1 INTRODUCTION One decade after the publication of the first genome-wide association study (GWAS), hundreds of genetic polymor- phisms have been associated with different complex diseases, including numerous immune-mediated disorders (Parkes, Cortes, van Heel, & Brown, 2013, Welter et al., 2014). How- ever, in most of the described risk loci, it is still challeng- ing to identify the causal gene/s. GWAS evidenced the high number of low-impact genetic variants predisposing to dis- ease risk and, notoriously, the wide genetic overlap among immune disorders. This shared genetic background influ- ences the existence of common pathogenic mechanisms and it has been used to find new susceptibility variants through cross-disease comparison studies (Coenen et al., 2009; Ellinghaus et al., 2012; Eyre et al., 2010; Festen et al., 2011; Smyth et al., 2008; Zhernakova et al., 2011). The suc- cessfully addressed Immunochip Project included 186 loci Ann Hum Genet. 2018;1–9. © 2018 John Wiley & Sons Ltd/University College London 1 wileyonlinelibrary.com/journal/ahg