Genetics of bipolar disorder

Area of Science:

• Psychiatric Genetics
• Genomic Medicine
• Clinical Validity

Background:

• Bipolar disorder is a complex genetic condition with an unknown transmission mode.
• Genome-wide studies identified common single nucleotide polymorphisms (SNPs) associated with bipolar disorder.
• Rare structural variants and mutations in Mendelian disorders with psychiatric symptoms are also recognized.

Purpose of the Study:

• To evaluate the current state of genetic testing for bipolar disorder.
• To assess the clinical utility and validity of common variant genetic testing.
• To compare common variant testing with established testing for Mendelian disorders.

Main Methods:

• Review of genome-wide association studies (GWAS) for bipolar disorder.
• Analysis of findings from population-based genome-wide studies in psychiatric disorders.
• Evaluation of established criteria for genetic test introduction: analytical validity, clinical validity, and clinical utility.

Main Results:

• Common variants explain a small percentage of bipolar disorder's genetic risk, with inconclusive functional consequences.
• Associated SNPs are not disease-specific, and most carriers of risk alleles remain healthy.
• Testing for chromosomal and monogenic Mendelian disorders is established, but common variant testing for psychiatric disorders is controversial.

Conclusions:

• Current genetic testing for common variants in bipolar disorder does not meet established criteria for clinical validity and utility.
• Further research is required before widespread clinical implementation of genetic testing for common variants in psychiatric disorders.
• Rare variants and Mendelian disorders with psychiatric manifestations offer alternative genetic insights but require distinct testing approaches.