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Progress and pitfalls: bipolar molecular linkage studies

W Berrettini1

  • 1Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia 19104, USA. wadeb@mail.med.upenn.edu

Journal of Affective Disorders
|December 19, 1998
PubMed
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This review covers the history of molecular genetic linkage studies for bipolar disorder (BP disorder), highlighting confirmed genetic linkages and future research recommendations. It emphasizes the complexity of BP disorder genetics, likely involving multiple genes.

Area of Science:

  • Genetics
  • Psychiatry
  • Molecular Biology

Background:

  • Bipolar disorder (BP disorder) has a complex genetic basis.
  • Understanding genetic linkage is crucial for identifying susceptibility genes.
  • Previous studies have faced challenges due to the polygenic nature of the disorder.

Purpose of the Study:

  • To review the historical development of molecular genetic linkage studies in bipolar disorder.
  • To discuss key genetic concepts and criteria for establishing linkage.
  • To present confirmed genetic linkages and recommendations for future research.

Main Methods:

  • Review of historical molecular genetic linkage studies.
  • Discussion of genetic concepts: linkage, lod scores, non-parametric statistics.

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  • Analysis of criteria for confirming genetic linkage, including independent replication.

    • Main Results:

    • Several valid genetic linkages for bipolar disorder have been identified and confirmed.
    • Confirmed linkages include specific genomic regions: 18p11, 18q22, 21q21, Xq26, and 4pter.
    • The study acknowledges the challenges in universally confirming linkages due to multiple genes with small effects.

    Conclusions:

    • Independent confirmation is essential for declaring valid genetic linkages in bipolar disorder.
    • Future studies should consider the polygenic nature of bipolar disorder when designing linkage analyses.
    • Recommendations are provided for advancing genetic linkage research in bipolar disorder.