Potential use of clinical polygenic risk scores in psychiatry – ethical implications and communicating high polygenic risk

Abstract

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in research and clinical contexts could have ethical implications , with a particular focus on potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder . While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations.

Precision Prostate Cancer Screening with a Polygenic Risk Score

“…Combining PRS with PSA has shown the potential for increasing the performance of stand-alone screening (18 (43). Our approach is easily adaptable to nationalities other than Estonia by using population background information data of other genetically similar populations.…”

Psychosocial implications of living with familial risk of a psychiatric disorder and attitudes to psychiatric genetic testing: A systematic review of the literature

“…Even though genetic testing is recommended in the assessment and treatment of autism spectrum disorders and intellectual disability, its current use is limited in clinical practice (Nurnberger et al, 1994). Current genomic testing focuses primarily on neurodevelopmental disorders, including chromosomal microarray plus genetic testing for Fragile X (Nurnberger et al, 1994), a rare monogenic disorder (Palk, Dalvie, de Vries, Martin, & Stein, 2019).…”

“…While psychiatric disorders are highly heritable, this is largely due to polygenic risk factors rather than rare monogenic variants. Acknowledging that polygenic risk scores (PRSs) currently lack predictive power and may never possess clinical utility for certain psychiatric disorders (Palk et al, 2019), it remains possible that in the future PRS may be developed for clinical use for conditions with high heritability such as schizophrenia and bipolar disorder (Palk et al, 2019). Khera et al (2018) estimate that individuals at the top end of the PRS distribution may have three to five times higher relative risk than the general population for certain conditions, with even higher relative risks for conditions with very high heritability such as schizophrenia (Khera et al, 2018).…”

“…It has also been argued that in the future, as the datasets supporting the development of such scores become larger, PRS may have clinical utility to assess risk for disease, subtypes of disease, and even treatment response (Fullerton & Nurnberger, 2019). PRS may also be able to aid differential diagnosis (Palk et al, 2019), given that PRS have recently been used to identify both shared genetic components and genetic differences between schizophrenia and bipolar disorder (Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2018).…”

Polygenic risk scores and their potential clinical use in psychiatry: are we there yet?

“… 3 The discriminatory abilities and clinical applicability of PRSs are expected to significantly improve with more powerful base GWAS, 4 a focus on studies of diverse ethnic populations, and the development of more sophisticated methods for their calculations. Importantly, given their potential groundbreaking clinical applications, it is imperative that researchers responsibly discuss and explain the limitations of PRSs to the lay public and be aware of the ethical implications these scores may have to society, 5 including stigmatization and a potentially harmful reductive view of psychiatric disorders.…”