Auteur Topic: Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease  (gelezen 1947 keer)


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Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease
« Gepost op: juli 23, 2009, 14:09:13 »
Abstract artikel.

Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease
Paola Foraboscoa, b, Susan L. Neuhausenc, Luigi Grecod, Åsa Torinsson Naluaie, Cisca Wijmengaf, Päivi Saavalaineng, Richard S. Houlstonh, Paul J. Ciclitirai, Marie-Claude Babronj, Cathryn M. Lewisa, k

a King's College London, Department of Medical and Molecular Genetics, London, UK;
b Istituto di Genetica delle Popolazioni - CNR, Sassari, Italy;
c Department of Epidemiology, University of California Irvine, Irvine, Calif., USA;
d Department of Pediatrics, European Laboratory for Food Induced Diseases, University 'Federico II', Naples, Italy;
e Department of Medical and Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Göteborg, Sweden;
f Genetics Department, University Medical Centre Groningen and University of Groningen, Groningen, The Netherlands;
g Department of Medical Genetics and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland;
h Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK;
i Department of Gastroenterology, King's College London, St Thomas' Hospital, London, UK;
j INSERM UMR535 and Université Paris Sud, Villejuif, France, and
k King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK

Key Words:
Celiac disease
Genome-wide linkage analysis
Genome-wide association analysis
Dermatitis herpetiformis

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.

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.

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.

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.

Groeten, Ine