Linkage of bipolar disorder to chromosome 18 has been suggested by several studies, but the results have been inconsistent and poorly-localized. Our analysis of the relationship between clinical features and allele-sharing on chromosome 18q22 has identified a region linked to bipolar disorder with a lod of 4.85 and a 1-lod confidence interval of ∼9 cM. We have anchored this interval to the human draft sequence, and have identified a ∼5 MB candidate region. Our strategy for identifying the gene that accounts for this linkage finding uses SNP-based association analysis to sample essentially all of the common genetic variation occurring in and near each gene in the region. Our preliminary computational annotation of the human draft sequence has identified approximately 50 known or predicted genes. Our analysis of 32 SNPs mapped to a finished BAC in the region indicates that background linkage disequilibrium is detectable in our study populations at ∼60 kb. Based on this, we have developed an initial set of 50 common SNPs that are being used to screen all genes in the region for trait-marker association in 3 samples of case-parent triads. Our data indicate that SNP-based association analysis is feasible, and illustrate one strategy for systematically evaluating marker-trait association within a candidate region.
|Original language||English (US)|
|Number of pages||1|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|State||Published - Oct 8 2001|
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience