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

By R. Segurado, S. Detera-Wadleigh, Douglas F. Levinson, Cathryn M. Lewis, M. Gill, J. Nurnberger, N. Craddock, J. DePaulo, M. Baron, E. Gershon and 68 more. American Journal of Human Genetics, 2003

604 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/69bc9847daa19463ea739e105f70dafa1d239d32

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease (2014, background): “The observations of multiple genome-wide significant or suggestive linkage signals for disorders, that do not readily replicate between studies but which are not randomly distributed across the genome[17,18] is compatible with the existence of multiple risk alleles of moderate effect that would impl”
Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. (2003, methodology): “Since there were too few studies that used each alternative definition of the phenotype to permit separate GSMAs (as was done for bipolar disorder in the following article in this series [ Segurado et al. 2003 {in this issue}]), we used the analysis from each study that came closest to the predomin”
The genetics of schizophrenia and bipolar disorder: dissecting psychosis (2005, methodology): “However, the more extensive and detailed meta-analysis of Segurado et al 102 conducted using the same bin ranking methodology as used in the meta-analysis of schizophrenia scans 14 did not find genome-wide significant evidence for linkage but provided a more modest level of support for regions on ch”
Convergent evidence for impaired AKT1-GSK3β signaling in schizophrenia (2004, background): “9 ), and a recent rank-based genome scan meta-analysis of 18 BPD genome scan data sets provided additional support for linkage in the combined data for the same locu”