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- Mascalzoni, Deborah, 1973-, et al.
(author)
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Balancing scientific interests and the rights of participants in designing a recall by genotype study
- 2021
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In: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 29:7, s. 1146-1157
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Journal article (peer-reviewed)abstract
- Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants' views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology.
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| 2. |
- Mascalzoni, Deborah, 1973-, et al.
(author)
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Participant perspective on the recall-by-genotype research approach : a mixed-method embedded study with participants of the CHRIS study.
- 2023
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438.
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Journal article (peer-reviewed)abstract
- Recall-by-genotype (RbG) research recruits participants previously involved in genetic research based on their genotype. RbG enables the further study of a particular variant of interest, but in recalling participants, it risks disclosing potentially unwanted or distressing genetic information. Any RbG strategy must therefore be done in a manner that addresses the potential ethical and social issues. As part of an RbG pilot on the penetrance of Parkinson's disease variants, we conducted an empirical mixed-method study with 51 participants of the Cooperative Health Research in South Tyrol (CHRIS) study to understand participant views on RbG research approach. Participants were disclosed the disease under investigation but not the individual variant carrier status. Results showed that participants filtered the information received through personal experience and enacted mechanisms to address the concerns raised by invitation by resorting to personal resources and the support provided by experts. While the non-disclosure of the Parkin variant carrier status was deemed acceptable, disclosing the disease under study was important for participants. Participant preferences for disclosure of the disease under investigation and the carrier status varied according to how the knowledge of individual carrier status was perceived to impact the participant's life. This study provided insights into participant response to the RbG research approach, which are relevant for RbG policy development. A suitable communication strategy and granular options addressing preferences for invitation in the original informed consent are critical for an ethically informed RbG policy.
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| 3. |
- Prasuhn, Jannik, et al.
(author)
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Task matters-challenging the motor system allows distinguishing unaffected Parkin mutation carriers from mutation-free controls
- 2021
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In: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 86, s. 101-104
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Journal article (peer-reviewed)abstract
- Background: Heterozygous carriers of Parkin mutations are suggested to be at risk of developing Parkinson's disease, while biallelic variants are associated with typical autosomal recessive early-onset PD. Investigating unaffected heterozygous mutation carriers holds the potential of a deeper understanding of monogenic PD and has implications for PD in general, in particular regarding the prodromal phase.Objectives: To discriminate healthy Parkin mutation carriers from healthy non-mutation carriers using a multimodal approach.Methods: Twenty-seven healthy heterozygous Parkin mutation carriers (13 female. age: 48 +/- 13 years) and 24 healthy non-mutation carriers (14 female. age: 48 +/- 15 years) from the CHRIS study (Cooperative Health Research in South Tyrol) were recalled based on their genetic profile and underwent a blinded assessment of motor and non-motor PD symptoms, transcranial sonography and sensor-based posturography and gait analyses under different conditions with increasing difficulty. For the latter, gradient-boosted trees were used to discriminate between carriers and non-carriers. The classification accuracy and the area under the curve of the receiver-operator characteristics curve were calculated.Results: We observed no differences concerning motor or non-motor symptoms and substantia nigra hyperechogenicity. The best gradient-boosted trees-based model on posturography measurements (tandem feet, eyes closed, firm surface), however, showed a classification accuracy of up to 86%. The best-performing gradientboosted trees-based model for gait analyses showed a balanced accuracy of up to 87% (dual-tasking).Conclusions: Sensor-based quantification of movements allows to discriminate unaffected heterozygous mutation carriers from mutation-free controls. Thereby, it is crucial to challenge the motor system with more difficult tasks to unmask subtle motor alterations.
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