Clinical evaluation of potentially actionable ‘additional findings’ in inherited cardiac condition genes (SCARFE)

Summary

Personal whole genome sequencing is a recently available tool for investigation of rare disease and cancer. In addition to finding genetic causes for the disease under investigation, it is possible to look for other genetic variants associated with risk of future disease, or disease that is present but concealed because it is not always symptomatic. This study will focus on a major group of such conditions: inherited heart conditions (IHC), which can be diagnosed using standard clinical tests.

A key question is whether such findings are in fact associated with disease when identified in a population that is not known to have the condition in question.

The study is based on the NIHR BioResource for Rare Disease (BRRD); participants have consented to genome sequencing, sharing anonymised data, and to re-contact for future studies. We will screen participant genomes for variants associated with an IHC; the BRRD team will then match cases with controls who do not have a variant. We will use two-step approach process to allow pre-opt out of receiving genetic or health information.

Potential participants will attend a study visit in Oxford, when the implications of participation, including that a potential diagnosis of an IHC might be made, will be discussed before consent is sought. A medical and family history will be taken. Participants will be offered clinical tests based on cardiac imaging and electrocardiogram. Participants and investigators will be blind to genetic status during clinical investigation; at the end of the visit we will unblind and advise participants of the results of their genetic and clinical tests.

We will also ask participants to complete questionnaires during the study visit, and by phone 2 weeks, 3 months and one year after the visit. Some participants will be invited to take part in a semi-structured interview.

Organisation: This study was organised by Professor Hugh Watkins of the Radcliffe Department of Medicine at the University of Oxford. 

Participation: 9 rare disease BioResource participants took part in the study in 2017.