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

Nature Genetics volume 12, pages 436–441 (1996)Cite this article

Abstract

Manic-depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression1. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica2,3 to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome of two Costa Rican BPI pedigrees (Mclnnes et al., submitted). We considered only individuals who full-filled 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 lod 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.

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Authors and Affiliations

  1. Neurogenetics Laboratory, University of California San Francisco, San Francisco, California, 94143, USA

    Nelson B. Freimer, Michael A. Escamilla, Susan K. Service, Lauren B. Smith, Siamak Baharloo, Kathleen Blankenship & David J. Tyler

  2. Center for Neurobiology and Psychiatry, Department of Psychiatry, University of California San Francisco, San Francisco, California, 94143, USA

    Nelson B. Freimer, Victor I. Reus, Michael A. Escamilla, Susan K. Service, Alvaro Gallegos, Steven Batki, Sophia Vinogradov & Samuel H. Barondes

  3. Programs in Genetics and Biomedical Sciences, University of California, San Francisco, San Francisco, California, 94143

    Nelson B. Freimer & L. Alison Mclnnes

  4. Cell and Molecular Biology Research Center and Escuela de Medicina (P.L) Universidad de Costa Rica, San Jose, Costa Rica

    Mitzi Spesny, Pedro Leon, Sandra Silva, Eugenia Rojas & Eduardo Fournier

  5. Hospital Calderon Guardia, San Jose, Costa Rica

    Alvaro Gallegos & Luis Meza

  6. Department of Psychiatry, University of California San Francisco, San Francisco General Hospital, San Francisco, California, 94110, USA

    Steven Batki

  7. Généthon 1 rue de l'Internationale, 91000, Evry, France

    Jean Weissenbach

  8. Unité de Génétique Moléculaire Humaine, CNRS URA 1445, Institut Pasteur, 75724, Paris Cédex, France

    Jean Weissenbach

  9. Department of Clinical Genetics, Erasmus University, Rotterdam

    Lodewijk A. Sandkuijl

  10. Department of Human Genetics, Leiden University, Department of Medical Genetics, Groningen University, The Netherlands

    Lodewijk A. Sandkuijl

Authors
  1. Nelson B. Freimer
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  2. Victor I. Reus
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Correspondence to Nelson B. Freimer.

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Freimer, N., Reus, V., Escamilla, M. et al. Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23. Nat Genet 12, 436–441 (1996). https://doi.org/10.1038/ng0496-436

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