Implementing secondary findings analysis in a genetic and environmental research study.

Abstract

Optimizing return of secondary findings (SFs) in research settings requires an understanding of the complexities and challenges. Genome sequence was generated for 4737 participants in a genetic and environmental health study, and 4630 of them consented to SF return. Variants in the American College of Medical Genetics and Genomics v3.0 genes were classified using the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria with ClinGen-approved modifications. Eighty-six variants were eligible for return to 102 participants. Average time to initial recontact attempt was 5.8 years. Recontact attempts reached 95 of 102 individuals. Results were returned to 57 participants. The remainder passively declined (25), actively declined (11), were lost to follow-up (5), were deceased (3), or had prior knowledge of the result (1). Return of results was positively associated with education status (2 × 3 C², P = .0035). The interest in receiving SFs was high at the time of consenting, but a clinically validated result was returned to just over half of the individuals with an SF. Approximately 1 in 3 participants with an SF who had consented to receive them subsequently actively or passively declined receipt of the result. Given the health importance of return of SF, minimizing the time from consent to results return and tailoring outreach to education level may optimize uptake of SF return.