Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

Area of Science:

• Genetics
• Psychiatry
• Neuroscience

Background:

• Early-onset bipolar disorder (BD) presents unique challenges in diagnosis and treatment.
• Understanding the genetic underpinnings of early-onset BD is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the association of a candidate genetic risk score (GRS) with early-onset bipolar disorder (BD).
• To explore the role of specific single-nucleotide polymorphisms (SNPs) and their corresponding genes in early-onset BD.

Main Methods:

• A genetic risk score (GRS) analysis was conducted using 8 previously identified BD-associated SNPs.
• Genotyping was performed on samples from the Treatment of Early Age Mania (TEAM) study, the Mayo Clinic Bipolar Biobank, and healthy controls.
• Association analyses included GRS, individual SNP, and haplotype analyses comparing early-onset BD cases with controls.

Main Results:

• The GRS analysis revealed a significant association with early-onset BD (P = .01).
• Gene-level haplotype analysis suggested an association between early-onset BD and a CACNA1C haplotype (P = .01).
• A nominally significant association was observed for SNP rs10848632 in CACNA1C with early-onset BD (P = .017), though it did not withstand correction for multiple comparisons.

Conclusions:

• Previously identified genetic risk loci for BD, especially CACNA1C, appear to be involved in early-onset BD.
• The genetic contribution of these loci may be more pronounced in early-onset BD compared to late-onset forms.