Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults

Abstract

Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD. Methods: A final sample of 185 young, high-risk German adults (aged 18-35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes. Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls. Biere et al. Risk Stratification for Bipolar Disorder Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.

A Predictive Model of Risk Factors for Conversion From Major Depressive Disorder to Bipolar Disorder Based on Clinical Characteristics and Circadian Rhythm Gene Polymorphisms

“…The conversion rate of our study was 12.7%, similar to a prospective cohort study which showed the rate of conversion from MDD to BD in 3 years was 12.4% ( 35 ). The conversion rates have been reported as between 2.5 and 15.4% in follow-up intervals of 3–9 years ( 37 ). The conversion rate of our study was consistent with these studies.…”

Emerging trends in gene and bipolar disorder research: a bibliometric analysis and network visualisation

“…Twelve of the differentially methylated regions identified in the former study overlapped with the loci identified by a GWAS of bipolar disorder (Stahl et al, 2019). The polygenic risk score derived from GWAS was used to explore the genetic risk of bipolar disorder (Biere et al, 2020). In addition, despite the lack of clear evidence from GWAS linking bipolar disorder to circadian rhythm disruption (Walker et al, 2020) or any of the clock genes (McCarthy, 2019) in humans, research on this topic is growing.…”