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A linkage study of bipolar illness

W H Berrettini1, T N Ferraro, L R Goldin

  • 1Department of Psychiatry and Human Behavior, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa, USA. berrettiniw@jeflin.tju.edu

Archives of General Psychiatry
|January 1, 1997
PubMed
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Researchers identified a significant genetic linkage for bipolar disorder (BP) susceptibility near the centromere of chromosome 18. This finding suggests a specific gene region contributing to the heritability of BP illness.

Area of Science:

  • Genetics
  • Psychiatry
  • Molecular Biology

Background:

  • Genetic epidemiological studies indicate bipolar disorder (BP) has a heritable component.
  • However, specific inherited risk factors for BP remain unidentified.
  • This study aimed to localize BP susceptibility loci using linkage strategies.

Purpose of the Study:

  • To identify the chromosomal location of genes predisposing individuals to bipolar disorder.
  • To conduct a genome-wide search for linkage of bipolar disorder susceptibility loci.
  • To analyze genetic linkage data using various statistical models and definitions of the bipolar spectrum.

Main Methods:

  • Linkage analysis was performed on 22 bipolar disorder families comprising nearly 400 individuals.
  • Genetic linkage was assessed using autosomal dominant and recessive models with varying penetrance.

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  • Analysis included 310 DNA markers across multiple chromosomes, with a focus on chromosome 18.

    • Main Results:

    • No compelling linkage evidence was found using standard lod score analyses for most examined loci.
    • Model-independent analysis revealed statistically significant evidence for a BP susceptibility gene near the pericentromeric region of chromosome 18 (P < .0001).
    • Affected sibling pair analysis corroborated these findings, showing evidence for linkage in the same region (P < .00008).

    Conclusions:

    • The study implies the existence of a bipolar disorder susceptibility gene near the centromere of chromosome 18.
    • Subsequent independent studies have published confirmatory findings.
    • This suggests the discovery of a valid genetic linkage for bipolar disorder.