title: Meta-analysis of genome-wide linkage studies in celiac disease.
abstract: OBJECTIVE
  A meta-analysis of genome-wide linkage studies allows us to summarize the extensive information available from family-based studies, as the field moves into genome-wide association studies.
  
  
  METHODS
  Here we apply the genome scan meta-analysis (GSMA) method, a rank-based, model-free approach, to combine results across eight independent genome-wide linkages performed on celiac disease (CD), including 554 families with over 1,500 affected individuals. We also investigate the agreement between signals we identified from this meta-analysis of linkage studies and those identified from genome-wide association analysis using a hypergeometric distribution.
  
  
  RESULTS
  Not surprisingly, the most significant result was obtained in the HLA region. Outside the HLA region, suggestive evidence for linkage was obtained at the telomeric region of chromosome 10 (10q26.12-qter; p = 0.00366), and on chromosome 8 (8q22.2-q24.21; p = 0.00491). Testing signals of association and linkage within bins showed no significant evidence for co-localization of results.
  
  
  CONCLUSIONS
  This meta-analysis allowed us to pool the results from available genome-wide linkage studies and to identify novel regions potentially harboring predisposing genetic variation contributing to CD. This study also shows that linkage and association studies may identify different types of disease-predisposing variants.
authors.affiliation: King's College London, Department of Medical and Molecular Genetics, London, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Forabosco
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Luigi
authors.initials: L
authors.lastname: Greco
authors.forename: Asa Torinsson
authors.initials: AT
authors.lastname: Naluai
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Paivi
authors.initials: P
authors.lastname: Saavalainen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Ciclitira
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Babron
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
mesh_terms: D002446:Celiac Disease / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D002888:Chromosomes, Human, Pair 19; D008040:Genetic Linkage; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans