Implementing secondary findings analysis in a genetic and environmental research study

Area of Science:

• Genomics
• Clinical Genetics
• Bioethics

Background:

• Research studies generate secondary findings (SFs) with potential health implications.
• Returning SFs involves complex logistical and ethical considerations.
• Understanding participant engagement with SF return is crucial for optimizing research practices.

Purpose of the Study:

• To investigate the complexities and challenges associated with returning secondary findings (SFs) in a research setting.
• To analyze the rate of successful return of SFs and factors influencing participant uptake.
• To identify strategies for improving the efficiency and effectiveness of SF return processes.

Main Methods:

• Generated genome sequences for 4737 participants in a health study.
• Obtained consent for SF return from 4630 participants.
• Classified variants using established American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria with ClinGen modifications.

Main Results:

• Eighty-six variants were eligible for return to 102 participants.
• Average time to initial recontact was 5.8 years; 95 individuals were reached.
• Results were returned to 57 participants; significant proportions declined or were lost to follow-up.
• Return of results was positively associated with education status (P = .0035).

Conclusions:

• High initial interest in SFs contrasts with a lower rate of actual result delivery.
• A substantial proportion of participants who consented later declined SF receipt.
• Optimizing SF return requires minimizing return time and tailoring outreach based on education level.