A Reanalysis of 409 European-Ancestry and African American Schizophrenia Pedigrees Reveals Significant Linkage to 8p23.3 With Evidence of Locus Heterogeneity

Holliday, E. G., Mowry, B. J. and Nyholt, D. R. (2008) A Reanalysis of 409 European-Ancestry and African American Schizophrenia Pedigrees Reveals Significant Linkage to 8p23.3 With Evidence of Locus Heterogeneity. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B 7: 1080-1088. doi:10.1002/ajmg.b.30722


Author Holliday, E. G.
Mowry, B. J.
Nyholt, D. R.
Title A Reanalysis of 409 European-Ancestry and African American Schizophrenia Pedigrees Reveals Significant Linkage to 8p23.3 With Evidence of Locus Heterogeneity
Journal name American Journal of Medical Genetics Part B: Neuropsychiatric Genetics   Check publisher's open access policy
ISSN 1552-4841
Publication date 2008-10-05
Sub-type Article (original research)
DOI 10.1002/ajmg.b.30722
Open Access Status Not Open Access
Volume 147B
Issue 7
Start page 1080
End page 1088
Total pages 9
Editor Ming T. Tsuang
Stephen V. Faraone
Place of publication New York, N.Y.
Publisher Wiley-Liss
Language eng
Subject 321204 Mental Health
C1
920209 Mental Health Services
111714 Mental Health
Abstract The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups. © 2008 Wiley-Liss, Inc.
Keyword psychiatry
mental disorders
genetics
epidemiology
genetic susceptibility
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Published Online: 24 Mar 2008

Document type: Journal Article
Sub-type: Article (original research)
Collection: 2009 Higher Education Research Data Collection
 
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Created: Wed, 01 Apr 2009, 20:41:23 EST by Carmel Meir on behalf of School of Medicine