Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder

Ricardo Segurado, Sevilla D. Detera-Wadleigh, Douglas F. Levinson, Cathryn M. Lewis, Michael Gill, John I. Nurnberger, Nick Craddock, J. Raymond DePaulo, Miron Baron, Elliot S. Gershon, Jenny Ekholm, Sven Cichon, Gustavo Turecki, Stephan Claes, John R. Kelsoe, Peter R. Schofield, Renee F. Badenhop, J. Morissette, Hilary Coon, Douglas BlackwoodL. Alison Mclnnes, Tatiana Foroud, Howard J. Edenberg, Theodore Reich, John P. Rice, Alison Goate, Melvin G. McInnis, Francis J. McMahon, Judith A. Badner, Lynn R. Goldin, Phil Bennett, Virginia L. Willour, Peter P. Zandi, Jianjun Liu, Conrad Gilliam, Suh Hang Juo, Wade H. Berrettini, Takeo Yoshikawa, Leena Peltonen, Jouko Lönnqvist, Markus M. Nöthen, Johannes Schumacher, Christine Windemuth, Marcella Rietschel, Peter Propping, Wolfgang Maier, Martin Alda, Paul Grof, Guy A. Rouleau, Jurgen Del-Favero, Christine Van Broeckhoven, Julien Mendlewicz, Rolf Adolfsson, M. Anne Spence, Hermann Luebbert, Linda J. Adams, Jennifer A. Donald, Philip B. Mitchell, Nicholas Barden, Eric Shink, William Byerley, Walter Muir, Peter M. Visscher, Stuart Macgregor, Hugh Gurling, Gursharan Kalsi, Andrew McQuillin, Michael A. Escamilla, Victor I. Reus, Pedro Leon, Nelson B. Freimer, Henrik Ewald, Torben A. Kruse, Ole Mors, Uppala Radhakrishna, Jean Louis Blouin, Stylianos E. Antonarakis, Nurten Akarsu

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368 Scopus citations


Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.

Original languageEnglish
Pages (from-to)49-62
Number of pages14
JournalAmerican journal of human genetics
Issue number1
StatePublished - Jul 1 2003


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