Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia.

By Cathryn M. Lewis, Douglas F. Levinson, L. Wise, L. DeLisi, R. Straub, I. Hovatta, N. Williams, S. Schwab, A. Pulver, Stephen V. Faraone and 43 more. American Journal of Human Genetics, 2003

1,198 citations recorded by the source corpus.

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/69b8f969e9c9249c6e1728a05868c29773bb6728

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Citations in the corpus

Neuregulin 1 in neural development, synaptic plasticity and schizophrenia (2008, background): “Meta-analyses of whole-genome linkage scans identified 8p as a susceptibility locus for the disorde”
Heterogeneity testing in meta‐analysis of genome searches (2005, methodology): “This bin has given considerable evidence for linkage in some genome scans, but completely unimpressive results in several others [for details, see Lewis et al., 2003].”
Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. (2008, background): “Such peculiarities include the noncomplete concordance between monozygotic twins for both SZ (41%–65%) and BD (~60%),(2,4) which cannot be accounted for by only environmental factors.(3,5) Other complexities of major psychosis include a fluctuating disease course with periods of remission and relaps”
Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database (2008, neutral): “BDNF Zintzaras, 2007 270C/T 1,866 (5) 4,091 (8) T vs.”
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 III: Bipolar disorder. (2003, methodology): “Meta-analysis was performed as described by Wise et al. (1999) and in the first two articles of this series (Levinson et al. 2003 [in this issue]; Lewis et al. 2003 [in this issue]).”
Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration. (2014, neutral): “1, 15q26, and 5q21 for NCAM1, ST8SIA2, and ST8SIA4, respectively) (261, 269, 290).”