Psychiatric Polygenic Risk Scores Across Youth With Bipolar Disorder, Youth at High Risk for Bipolar Disorder, and...

Area of Science:

• Psychiatry
• Genetics
• Developmental Neuroscience

Background:

• Bipolar disorder (BD) in youth is understudied genetically.
• Polygenic risk scores (PRS) can quantify genetic susceptibility to disorders.

Purpose of the Study:

• To compare PRS for BD and other psychiatric disorders in youth with BD, youth at high risk (HR) for BD, and controls.
• To investigate the polygenic underpinnings of youth BD.

Main Methods:

• Constructed PRSs for BD, schizophrenia, major depressive disorder, and ADHD from adult genome-wide association studies.
• Analyzed PRSs in 344 European ancestry youths (13-20 years old): 136 with BD, 121 HR, and 87 controls.
• Used multinomial logistic regression, controlling for age, sex, and genetic principal components.

Main Results:

• Youth with BD had significantly higher BD-PRS than controls (OR=1.54, p=.006).
• HR youth had intermediate BD-PRS.
• BD-PRS explained 7.9% of phenotypic variance.
• PRSs for schizophrenia, MDD, and ADHD did not differ significantly among groups.

Conclusions:

• Adult-derived BD-PRS are elevated in youth with BD, supporting biological validation.
• The specificity of BD-PRS in youth was supported by non-significant differences in other psychiatric disorder PRSs.
• Findings suggest potential for early identification and diagnosis of youth BD.
• Future research should focus on early-onset BD and integrate genetic and environmental factors.