The genetics of bipolar disorder

Area of Science:

• Psychiatry
• Genetics
• Neuroscience

Background:

• Bipolar disorder is a mood disorder with significant heritability.
• Identifying specific susceptibility genes has been challenging due to complex genetics and limited models.
• Previous linkage studies yielded inconsistent results.

Purpose of the Study:

• To review the progress and challenges in identifying genes associated with bipolar disorder.
• To highlight the shift towards association studies and genome-wide approaches.
• To discuss the implications of polygenicity for future genetic research.

Main Methods:

• Review of linkage studies and candidate gene association studies.
• Evaluation of genome-wide association analysis (GWAS) findings.
• Discussion of genetic and phenotypic complexity.

Main Results:

• Several candidate genes (e.g., BDNF, DISC1) have shown associations but none are definitively established.
• Genome-wide association studies have begun to implicate specific genes (e.g., DGKH, CACNA1C, ANK3).
• Bipolar disorder is characterized by polygenicity, with many genes of small effect.

Conclusions:

• Association studies and GWAS are more powerful for detecting genes of modest effect in complex disorders like bipolar disorder.
• Large sample sizes are crucial for identifying polygenic risk loci.
• Further genetic dissection may reveal novel therapeutic targets for bipolar disorder.