title: Revisiting genome wide association studies (GWAS) in coeliac disease: replication study in Spanish population and expression analysis of candidate genes.
abstract: BACKGROUND
  Recent genome wide association studies (GWAS) on coeliac disease (CD) have identified risk loci harbouring genes that fit the accepted pathogenic model and are considered aetiological candidates.
  
  
  METHODS
  Using Taqman single nucleotide polymorphism (SNP) and expression assays, the study genotyped 11 SNPs tagging eight GWAS regions (1q31, 2q11-2q12, 3p21, 3q25-3q26, 3q28, 4q27, 6q25 and 12q24) in a Spanish cohort of 1094 CD patients and 540 controls, and performed expression analyses of candidate genes (RGS1, IL18R1/IL18RAP, CCR3, IL12A/SCHIP1, LPP, IL2/IL21-KIAA1109, TAGAP, and SH2B3) in intestinal mucosa from 29 CD children and eight controls.
  
  
  RESULTS
  Polymorphisms in 1q31, 2q11-2q12, and 3q25 showed association in our cohort, and also 3q28 and 4q27 when combined with a previous study. Expression levels of IL12A, IL18RAP, IL21, KIAA1109, LPP, SCHIP1, and SH2B3 were affected by disease status, but the correlation between genotype and mRNA levels was observed only in IL12A, LPP, SCHIP1, and SH2B3.
  
  
  CONCLUSIONS
  Expression differences between treated CD patients and controls along with SNP expression associations suggest a possible primary role for these four genes and their variants in pathogenesis. The lack of SNP effect in the remaining genes is probably a consequence of arbitrary candidate gene selection within association signals that are not based on functional studies.
authors.affiliation: Endocrinology Diabetes and Nutrition Research Group, Hospital de Cruces, Barakaldo, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Plaza-Izurieta
authors.forename: Ainara
authors.initials: A
authors.lastname: Castellanos-Rubio
authors.forename: Iñaki
authors.initials: I
authors.lastname: Irastorza
authors.forename: Nora
authors.initials: N
authors.lastname: Fernández-Jimenez
authors.forename: Galder
authors.initials: G
authors.lastname: Gutierrez
authors.forename: Jose Ramon
authors.initials: JR
authors.lastname: Bilbao
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013030:Spain