Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease

TY - JOUR

T1 - Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease

AU - Forabosco, Paola

AU - Neuhausen, Susan L.

AU - Greco, Luigi

AU - Naluai, Asa Torinsson

AU - Wijmenga, Cisca

AU - Saavalainen, Paivi

AU - Houlston, Richard S.

AU - Ciclitira, Paul J.

AU - Babron, Marie-Claude

AU - Lewis, Cathryn M.

PY - 2009

Y1 - 2009

N2 - 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. Conclusion: 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. Copyright (C) 2009 S. Karger AG, Basel

AB - 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. Conclusion: 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. Copyright (C) 2009 S. Karger AG, Basel

U2 - 10.1159/000228920

DO - 10.1159/000228920

M3 - Article

VL - 68

SP - 223

EP - 230

JO - Human Heredity

JF - Human Heredity

IS - 4

ER -