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 psychiatric research and clinical contexts could have ethical implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. 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.

Polygenic risk scores in the clinic: new perspectives needed on familiar ethical issues

“…The third reason is the existence of the research agenda that looks for genetic correlations between predisposition for psychiatric conditions and various sociobehavioral traits, such as alcohol use, antisocial behavior, and intelligence (reviewed in [ 94 ]). These efforts to link the genetics of medical conditions and social outcomes expands the potential relevance of being labeled as at high risk for a psychiatric condition, an expansion which may be very unwelcome to many, and which heightens the possibility that individuals may experience stigmatization because of such a label.…”

Genetic feedback for psychiatric conditions: Where are we now and where are we going

“…Although GPS have been used in clinical settings to inform risk of diabetes (Grant et al, 2013) and guide treatment decisions for heart disease (Kullo et al, 2016), GPS are still in the very early stages of being used as a risk assessment tool for psychiatric conditions. Currently, GPS only capture a small amount of variance in most psychiatric phenotypes (Lewis & Vassos, 2017;Palk et al, 2019), limiting their utility in clinical settings (Barr et al, 2020). Further, the integration of genotypic information for psychiatric conditions into clinical care and decision-making will likely pose a number of additional complications, related to the complex etiological pathways through which risk for psychiatric and substance use disorders unfolds.…”

“…There are a number of reasons why returning genotypic information regarding risk for psychiatric conditions may provide individuals with clinically valuable information. The hope is that the information can be used to motivate individuals to practice healthy lifestyle behaviors, take preventative measures (McBride, Koehly, Sanderson, & Kaphingst, 2010), be vigilant in recognizing symptoms for earlier diagnosis and intervention, and assist in treatment options (Lewis & Vassos, 2017;Palk, Dalvie, de Vries, Martin, & Stein, 2019). However, a recent meta-analysis suggests the current literature provides little to no evidence that receiving genotypic information influences behavior (Hollands et al, 2016).…”

A two-stage approach to identifying and validating modifiable factors for the prevention of depression

“…As we are increasingly able to quantify polygenic risk for depression 13 and potentially return this information to individuals in the future 14 , it becomes vital to expand knowledge of effective actionable measures for those identified at elevated risk. In addition to genetics, life history factors such as traumatic events are known to increase risk for depression 15 .…”