Two genetically distinct forms of bipolar affective disorder?

Area of Science:

• Human Genetics
• Psychiatric Genetics
• Molecular Biology

Background:

• Bipolar affective illness (BPD) is a complex psychiatric disorder with a significant genetic component.
• Previous studies have explored various genetic loci associated with BPD, but definitive causative genes remain elusive.
• Understanding the genetic architecture of BPD is crucial for developing targeted treatments and diagnostic tools.

Purpose of the Study:

• To investigate the genetic basis of bipolar affective illness (BPD) by analyzing inheritance patterns in multiple pedigrees.
• To determine potential linkage of BPD to the Human Leukocyte Antigen (HLA) complex.
• To differentiate potential genetic subtypes of BPD based on transmission patterns and genetic markers.

Main Methods:

• Family-based genetic linkage analysis was performed on five pedigrees with BPD and no father-son transmission.
• Two additional pedigrees with father-son transmission of BPD were analyzed for linkage to the HLA region.
• Lod scores were calculated to assess the statistical significance of linkage at a theta of 0.15.

Main Results:

• No linkage to HLA was found in five pedigrees with BPD and no father-son transmission, suggesting a potential X-linked or other unlinked dominant gene (designated BPD1).
• Two pedigrees with father-son transmission of BPD showed highly suggestive linkage to HLA (lod = 2.61), proposing a separate gene (BPD2).
• A crossover event in one HLA-A/B haplotype suggested the BPD2 locus might be in the 6p2-pter region of chromosome 6.

Conclusions:

• The genetic etiology of bipolar affective illness (BPD) appears heterogeneous, with at least two distinct forms identified.
• BPD1, characterized by the absence of father-son transmission, may be influenced by an X-linked or unlinked dominant gene.
• BPD2, exhibiting father-son transmission, is strongly linked to the HLA region on chromosome 6, potentially localizing to 6p2-pter.