Improved ethical guidance for the return of results from psychiatric genomics research

Abstract

There is an emerging consensus that genomic researchers should, at a minimum, offer to return to individual participants clinically valid, medically important, and medically actionable genomic findings (e.g., pathogenic variants in BRCA1) identified in the course of research. However, this is not a common practice in psychiatric genetics research. Furthermore, psychiatry researchers often generate findings that do not meet all of these criteria, yet there may be ethically compelling arguments to offer selected results. Here, we review the return of results debate in genomics research and propose that, as for genomic studies of other medical conditions, psychiatric genomics researchers should offer findings that meet the minimum criteria stated above. Additionally, if resources allow, psychiatry researchers could consider offering to return pre-specified “clinically valuable” findings even if not medically actionable – for instance, findings that help corroborate a psychiatric diagnosis, and findings that indicate important health risks. Similarly, we propose offering “likely clinically valuable” findings, specifically, variants of uncertain significance potentially related to a participant’s symptoms. The goal of this Perspective is to initiate a discussion that can help identify optimal ways of managing the return of results from psychiatric genomics research.

Psychiatric genetics researchers' views on offering return of results to individual participants

“…There is a growing international consensus that certain clinically relevant findings should be offered to individual participants in genomics research (MEXT et al, ; Bookman et al, ; Collins & Varmus, ; NHGRI, ; Fabsitz, McGuire, Sharp, Puggal, & Beskow, ; Genomics England, 2018; H3Africa, ; Indian Council of Medical Research, ; Jarvik et al, ; Middleton et al, ; NASEM, ; NBAC, ; Parliament of Estonia, ; Parliament of Finland, ; Weiner, ). However, return of results (RoR) is not a common practice in the field of psychiatric genetics and there is a dearth of empirical literature about how this issue should be managed in this field compared to other areas of genetics research (Lázaro‐Muñoz et al, ). The growing use of genomic testing in psychiatry research and the recently emerging body of knowledge about the genetic architecture of psychiatric disorders, brings this issue to the foreground in psychiatry research (Lee et al, ; McCarroll, Feng, & Hyman, ; Need & Goldstein, ; Ripke et al, ; Ripke, Sanders, & Kendler, ; Sullivan, Daly, & O'Donovan, ; Visscher, Brown, McCarthy, & Yang, ; Yuen et al, ).…”

“…Such issues include financial and technical challenges, obtaining adequate informed consent, respect for autonomy including the participants' right to know or not to know genetic information, respect for the interests of participants' family members, difficulty in determining the pathogenicity of variants, and the potential for genetic discrimination (Evans, ; Fernandez, Kodish, & Weijer, ; Foster & Sharp, ; Green et al, ; Jarvik et al, ; Klitzman et al, ; McGuire, Knoppers, Zawati, & Clayton, ; Ravitsky & Wilfond, ). However, there are unique aspects of psychiatry and psychiatric genomics that may need to be considered when developing practical and ethically sound policies for this field, including: the polygenic nature of psychiatric disorders, the important role of environmental factors in psychiatry, the large sample sizes necessary to obtain significant findings in this field, the high prevalence of mental health stigma which increases the risk for discrimination, and the emotional impact that disclosing genomic findings may have on individuals who may be at risk or diagnosed with a psychiatric disorder (Carson & Rothstein, ; Hoge & Appelbaum, ; Lázaro‐Muñoz et al, ; Singh & Rose, ). However, little empirical research exists to identify exactly what these issues are, and how they influence psychiatric genetics stakeholders' attitudes and perspectives about RoR and what are the pros and cons of RoR in this context.…”

Attitudes toward the right to autonomous decision‐making in psychiatric genetic testing: Controversial and context‐dependent

“…This is also reflected by the fact that almost 50% of respondents stated that researchers should actively search for known risk variants for other diseases. Testing for known risk variants during genetic research is the subject of ongoing debate (Lazaro‐Munoz et al, ). The findings of the present study inform this debate, suggesting that prior to testing, researchers and research participants must achieve a consensus concerning which conditions should be considered severe, and also the degree of preventability and treatability that should be available before disclosure is offered.…”

“…The findings of the present study inform this debate, suggesting that prior to testing, researchers and research participants must achieve a consensus concerning which conditions should be considered severe, and also the degree of preventability and treatability that should be available before disclosure is offered. Irrespective of whether genetic data are to be disclosed, psychiatric genetic researchers must provide potential study participants with information concerning the scientific value and clinical utility of the genetic information, as well as their analytical and clinical validity, particularly since these often fail to fulfill the standards required in the routine clinical setting (Lazaro‐Munoz et al, ).…”

The ethics of global psychiatric genomics: Multilayered challenges to integrating genomics in global mental health and disability—A position paper of the Oxford Global Initiative in Neuropsychiatric GenEthics (NeuroGenE)

“…Alongside scientific research into the genomics of physical conditions, ethical discussions have explored core issues around the protection of research participants (e.g., community consent and consultation) and scientists in low‐income countries (e.g., data‐sharing and capacity‐building), as well as the regulatory mechanisms of international collaborations (e.g., sample storage, ownership, and export; de Vries et al, ). Questions of genetic identity, responsibility, and the ethics of return of results have also been part of bioethical discussions within the clinical context (Easter, ; Jarvik et al, ; Knoppers, Joly, Simard, & Durocher, ; Lázaro‐Muñoz et al, ; Miller, Christensen, Giacomini, & Robert, ; Novas & Rose, ; Phelan, Yang, & Cruz‐Rojas, ).…”