A reanalysis of 409 European-Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity
Autor: | Bryan J. Mowry, Dale R. Nyholt, Elizabeth G. Holliday |
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Rok vydání: | 2008 |
Předmět: |
Genetic Linkage
Population Locus (genetics) Pedigree chart Biology White People Genetic Heterogeneity Cellular and Molecular Neuroscience Genetic linkage Locus heterogeneity medicine Humans Genetic Predisposition to Disease education Allele frequency Genetics (clinical) Genetics education.field_of_study Genetic heterogeneity medicine.disease Pedigree Black or African American Psychiatry and Mental health Genetics Population Sample size determination Sample Size Schizophrenia Chromosomes Human Pair 5 Lod Score Chromosomes Human Pair 7 Chromosomes Human Pair 8 |
Zdroj: | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. :1080-1088 |
ISSN: | 1552-485X 1552-4841 |
DOI: | 10.1002/ajmg.b.30722 |
Popis: | 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. |
Databáze: | OpenAIRE |
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