Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource...

Area of Science:

• Genomics
• Biobanking
• Clinical Genetics

Background:

• Millions have undergone genomic research, but few receive actionable findings.
• Returning genomic results (gRoR) presents logistical and ethical challenges.

Purpose of the Study:

• To analyze the yield and logistical aspects of returning actionable genomic findings from a large biobank cohort.
• To assess participant engagement and costs associated with a genomic result return protocol.

Main Methods:

• Analysis of genomic data from 36,417 Mass General Brigham Biobank participants (2017-2021).
• Offered confirmation and return of pathogenic and likely pathogenic variants (PLPVs) in 59 genes.
• Evaluated variant detection accuracy of genotyping (GT) versus genome sequencing (GS) and participant disclosure preferences.

Main Results:

• Genotyping (GT) showed high false positive rates (44.9%) and missed variants (72.0%) compared to sequencing (GS).
• Verified PLPVs were found in 1% (GT) and 2.5% (GS) of the cohort.
• 37.5% of participants declined disclosure of actionable PLPVs; 76.3% were unaware of their variant status.

Conclusions:

• Genomic sequencing offers higher accuracy for detecting actionable variants than genotyping.
• Participant consent and variant disclosure preferences significantly influence gRoR program implementation.
• The cost per confirmed and disclosed PLPV was substantial ($3,224), highlighting the need for efficient gRoR strategies.