Polygenic risk scores may be useful in finding bipolar disorder link in adults, offspring

Using polygenic risk scores to determine likelihood of parental bipolar disorder passing to offspring is promising but unproven, according to a community-based case-control longitudinal study published in JAMA Psychiatry.

“In this study, we evaluated whether parents with BD and their offspring had specifically increased BD PRS [polygenic risk scores] compared with PRSs for depression, schizophrenia, and ADHD,” Boris Birmaher, MD, of Western Psychiatric Hospital at the University of Pittsburgh School of Medicine, and colleagues wrote.

“Also, for the first time in the literature to our knowledge, we examined pathways by which parental diagnosis of BD and parental BD PRS influenced the risk for offspring to develop BD.”

Researchers sought to evaluate the specific association of BD PRSs regarding familial transmission and validity of pediatric BD, as finding any genetic contributions to the transmission of BD from parents to offspring may provide a clearer picture of the risk.

Birmaher and colleagues collected data from 745 participants (336 parents, 409 children) enrolled in the Pittsburgh Biological Offspring Study, which included parents with BD I/II and their offspring, as well as parents without BD and their offspring. Participants were recruited between March 2001 and May 2007, with data analysis occurring from December 2020 to September 2021. PRSs were considered for BD, major depressive disorder, schizophrenia and ADHD.

In all, 156 parents with BD I/II and 180 parents without BD, 251 offspring of parents with BD and 158 offspring of parents without BD European ancestry were included in the study. Participants were assessed six to seven times over a mean follow-up period of 13 years. Retention rate for the entire length of the study was 84%.

The researchers evaluated participants using standardized interviews without regard to whether a parent was diagnosed with BD. DNA was extracted from saliva and genotyped. PRSs were constructed based on independent large-scale genome-wide association studies.

Results showed more offspring of parents with BD developed BD and depression compared with offspring of parents without BD diagnosis. PRSs for BD were elevated for both parents and offspring with BD compared to parents and offspring without BD.

In a model combining parental and offspring BD PRS, scores for offspring were fully predicted by that of their parents.

Data also revealed no significant differences in polygenic risk scores between study groups regarding major depressive disorder, schizophrenia and ADHD in either parents or offspring, and the above-mentioned diagnoses were not significantly associated with emergence of BD.

“Although promising, given the small associations, BD PRS is not yet suitable for clinical use to determine individual risk of BD,” Birmaher and colleagues wrote.

“However, as suggested by the literature when the methods to derive the PRS improve and the discovery samples become larger, BD PRS has the potential to be useful to predict BD in at-risk populations, inform differential diagnosis (eg, with ADHD or unipolar MDD) and response to treatment, and use in research studies of at-risk youth and youth with BD.”