Person-level contributions of bipolar polygenic risk score to the prediction of new-onset bipolar disorder in at-risk offspring.
J Affect Disord
; 368: 359-365, 2024 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-39299598
ABSTRACT
BACKGROUND:
Previous work indicates that polygenic risk scores (PRS) for bipolar disorder (BD) are elevated in adults and youth with BD, but whether BD-PRS can inform person-level diagnostic prediction is unknown. Here, we test whether BD-PRS improves performance of a previously published risk calculator (RC) for BD.METHODS:
156 parents with BD-I/II and their offspring ages 6-18 were recruited and evaluated with standardized diagnostic assessments every two years for >12 years. DNA was extracted from saliva samples, genotyping performed, and BD-PRS calculated based on a 2021 meta-analysis. Using a bootstrapped and cross-validated penalized Cox regression, we assessed whether BD-PRS (alone and interacting with clinical variables) improved RC performance.RESULTS:
Of 227 offspring, 38 developed BD during follow-up. The penalized regression selected BD-PRS and interactions between BD-PRS and parental age at mood disorder onset (AAO), depression, and anxiety. The resulting RC discriminated offspring who developed BD (vs. those that did not) with good accuracy (AUC = 0.81); removing BD-PRS and its interaction terms was associated with a significant decrement to the AUC (decrement = 0.07, p = 0.039). Further exploration of selected interaction terms indicated that all were significant (p-values<0.02), indicating that BD-PRS has a larger effect on the outcome in offspring with depression and anxiety, whose affected parent had a younger AAO.CONCLUSIONS:
The addition of BD-PRS to clinical/demographic predictors in the RC significantly improved its accuracy. BD-PRS predicted BD on the person-level, particularly in offspring of parents with earlier AAO who already had symptoms of anxiety and depression at intake.
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MEDLINE
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En
Ano de publicação:
2024
Tipo de documento:
Article