Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23

Nelson B. Freimer, Victor I. Reus, Michael A. Escamilla, L. Alison McInnes, Mitzi Spesny, Pedro Leon, Susan K. Service, Lauren B. Smith, Sandra Silva, Eugenia Rojas, Alvaro Gallegos, Luis Meza, Eduardo Fournier, Siamak Baharloo, Kathleen Blankenship, David J. Tyler, Steven Batki, Sophia Vinogradov, Jean Weissenbach, Samuel H. BarondesLodewijk A. Sandkuijl

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

Abstract

Manic-depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome of two Costa Rican BPI pedigrees (McInnes et al., submitted). We considered only individuals who fullfilled very stringent diagnostic criteria for BPI to be affected. The strongest evidence for a BPI locus was observed in 18q22-q23. We tested 16 additional markers in this region and seven yielded peak rod scores over 1.0. These suggestive lod scores were obtained over a far greater chromosomal length (about 40 cM) than in any other genome region. This localization is supported by marker haplotypes shared by 23 of 26 BPI affected individuals studied. Additionally, marker allele frequencies over portions of this region are significantly different in the patient sample from those of the general Costa Rican population. Finally, we performed an analysis which made use of both the evidence for linkage and for association in 18q23, and we observed significant lod scores for two markers in this region.

Original languageEnglish (US)
Pages (from-to)436-441
Number of pages6
JournalNature Genetics
Volume12
Issue number4
DOIs
StatePublished - Apr 1996

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