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

Lewis, C. O., Levinson, D., Wise, L., DeLisi, L., Straub, R. and Mowry, B. (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. American Journal of Human Genetics, 73 1: 34-48. doi:10.1086/376549


Author Lewis, C. O.
Levinson, D.
Wise, L.
DeLisi, L.
Straub, R.
Mowry, B.
Title Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2003
Sub-type Article (original research)
DOI 10.1086/376549
Volume 73
Issue 1
Start page 34
End page 48
Total pages 15
Editor Stephen T Warren
Place of publication USA
Publisher University of Chicago Press
Collection year 2003
Language eng
Subject C1
321021 Psychiatry
730211 Mental health
Abstract 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 (rootN[affected cases]). 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 (P-AvgRnk <.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, 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.
Keyword Genetics & Heredity
Susceptibility Locus
Linkage Analysis
Wide Scan
Vulnerability Locus
Genetic-linkage
Sibling Pairs
Schizoaffective Disorder
Chromosome 6q
Follow-up
Families
Q-Index Code C1
Additional Notes Authors of this document: Lewis, CM; Levinson, DF; Wise, LH; DeLisi, LE; Straub, RE; Hovatta, I; Williams, NM; Schwab, SG; Pulver, AE; Faraone, SV; Brzustowicz, LM; Kaufmann, CA; Garver, DL; Gurling, HMD; Lindholm, E; Coon, H; Moises, HW; Byerley, W; Shaw, SH; Mesen, A; Sherrington, R; ONeill, FA; Walsh, D; Kendler, KS; Ekelund, J; Paunio, T; Lonnqvist, J; Peltonen, L; ODonovan, MC; Owen, MJ; Wildenauer, DB; Maier, W; Nestadt, G; Blouin, JL; Antonarakis, SE; Mowry, BJ; Silverman, JM; Crowe, RR; Cloninger, CR; Tsuang, MT; Malaspina, D; Harkavy-Friedman, JM; Svrakic, DM; Bassett, AS; Holcomb, J; Kalsi, G; McQuillin, A; Brynjolfson, J; Sigmundsson, T; Petursson, H; Jazin, E; Zoega, T; Helgason, T.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2004 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 02:19:24 EST