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A systematic search for a bipolar predisposing locus on chromosome 5
S D Detera-Wadleigh1, W H Berrettini, L R Goldin
1Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
Summary
This study investigated chromosome 5 linkage for bipolar disorder in 14 families. Results suggest no significant linkage between chromosome 5 markers and bipolar illness in this cohort.
Area of Science:
- Genetics
- Psychiatric Disorders
- Molecular Biology
Background:
- Bipolar illness is a complex psychiatric disorder with a significant genetic component.
- Previous studies have suggested potential chromosomal regions associated with bipolar disorder, but definitive linkage has been elusive.
- Identifying specific genes or chromosomal regions linked to bipolar disorder is crucial for understanding its etiology and developing targeted treatments.
Purpose of the Study:
- To examine the potential linkage between markers on chromosome 5 and bipolar illness.
- To exclude or identify specific chromosomal regions associated with the genetic transmission of bipolar disorder within affected families.
Main Methods:
- Analysis of 24 genetic loci across chromosome 5 in 237 individuals from 14 pedigrees, including 69 affected with bipolar or schizoaffective disorder.
- Calculation of lod scores under dominant disease models, incorporating parameters for penetrance, disease gene frequency, age of onset, and phenocopy rate.
- Utilized multipoint analysis to refine the exclusion of chromosomal intervals.
Main Results:
- Lod scores were uniformly below -2.0 across all examined markers, indicating a lack of significant linkage under the assumption of genetic homogeneity.
- Multipoint analysis further supported the exclusion of intervals between markers.
- Analysis allowing for genetic heterogeneity did not identify any subset of families with linkage to the studied region.
Conclusions:
- The findings effectively exclude almost the entire mapped region of chromosome 5 as a significant contributor to bipolar illness in the studied pedigree series.
- This study significantly narrows down the search for bipolar disorder susceptibility genes by ruling out a substantial portion of chromosome 5.
- Further research should focus on other chromosomal regions or alternative genetic models to elucidate the genetic architecture of bipolar disorder.