Meta-analysis of genome-wide linkage studies in celiac disease.
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.
Forabosco
Paola
P
King's College London, Department of Medical and Molecular Genetics, London, UK.
Neuhausen
Susan L
SL
Greco
Luigi
L
Naluai
Asa Torinsson
AT
Wijmenga
Cisca
C
Saavalainen
Paivi
P
Houlston
Richard S
RS
Ciclitira
Paul J
PJ
Babron
Marie-Claude
MC
Lewis
Cathryn M
CM
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