A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees

L. Alison McInnes, Michael A. Escamilla, Susan K. Service, Victor I. Reus, Pedro Leon, Sandra Silva, Eugenia Rojas, Mitzi Spesny, Siamak Baharloo, Kathleen Blankenship, Amy Peterson, David Tyler, Norito Shimayoshi, Christa Tobey, Steven Batki, Sophia Vinogradov, Luis Meza, Alvaro Gallegos, Eduardo Fournier, Lauren B. SmithSamuel H. Barondes, Lodewijk A. Sandkuijl, Nelson B. Freimer

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genuine has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Original languageEnglish (US)
Pages (from-to)13060-13065
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Nov 12 1996
Externally publishedYes


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