Which Results to Return: Subjective Judgments in Selecting Medically Actionable Genes

Area of Science:

• Genomics
• Medical Genetics
• Bioethics

Background:

• Genomic advances prompt returning medically actionable gene (MAG) information to diverse populations.
• The selection of MAGs significantly influences the risks and benefits of genetic testing.
• Limited data exist on how decision-makers apply MAG selection criteria.

Purpose of the Study:

• To examine the process and criteria used by researchers in selecting MAGs for a general adult population genomic sequencing program.

Main Methods:

• Observation and audio recording of gene selection meetings.
• Analysis of meeting transcripts, gene scoring sheets, and handouts.
• Examination of a semiquantitative metric used for scoring genes on five criteria.

Main Results:

• The selection process was complicated by subjective judgments and conceptual challenges in defining and applying criteria.
• Limited evidence for fundamental scoring decisions posed challenges.
• Unplanned criteria emerged and were applied during the selection process.

Conclusions:

• Decision-makers must anticipate subjective judgments and limited evidence when identifying MAGs.
• Conceptual complexity in defining criteria is inevitable.
• The emergence of unplanned criteria requires adaptive strategies in gene selection for screening.