There is a pronounced gap in knowledge regarding the polygenic underpinnings of youth bipolar disorder (BD). This study aimed to compare polygenic risk score (PRS) in youth with BD, youth at high clinical and/or familial risk for BD (HR), and controls.
Participants include a total of 344 youth of European ancestry, ages 13-20 years old, including 136 youth with BD, 121 HR youth, and 87 controls. PRS for BD, schizophrenia (SCZ), major depressive disorder (MDD), or attention-deficit/hyperactivity disorder (ADHD) were constructed using independent genome-wide summary statistics from adult cohorts. Multinomial logistic regression was used to examine the association between each PRS and diagnostic status (BD vs. HR vs. controls). All genetic analyses controlled for age, sex, and 2 genetic principal components.
BD group showed significantly higher BD-PRS than the control group (OR=1.54, 95% CI=1.13-2.10, p=0.006), with the HR group numerically intermediate. BD-PRS explained 7.9% of phenotypic variance. PRS for SCZ, MDD, and ADHD were not significantly different among groups. Within the BD group, BD-PRS did not significantly differ in relation to BD subtype, age of onset, psychosis, and family history of BD.
BD-PRS derived from adult genome-wide summary statistics is elevated in youth with BD. Absence of significant between-group differences in PRS for other psychiatric disorders supports the specificity of BD-PRS in youth. Present findings add to the biological validation of BD in youth and could have implications for early identification and diagnosis. To enhance clinical utility, future GWAS that focus specifically on early-onset BD are warranted, as are studies integrating additional genetic and environmental factors.
Copyright © 2024. Published by Elsevier Inc.
