Identifying rare, medically relevant variation via population-based genomic screening in Alabama: opportunities and pitfalls

Academic Article


  • Purpose: To evaluate the effectiveness and specificity of population-based genomic screening in Alabama. Methods: The Alabama Genomic Health Initiative (AGHI) has enrolled and evaluated 5369 participants for the presence of pathogenic/likely pathogenic (P/LP) variants using the Illumina Global Screening Array (GSA), with validation of all P/LP variants via Sanger sequencing in a CLIA-certified laboratory before return of results. Results: Among 131 variants identified by the GSA that were evaluated by Sanger sequencing, 67 (51%) were false positives (FP). For 39 of the 67 FP variants, a benign/likely benign variant was present at or near the targeted P/LP variant. Variants detected within African American individuals were significantly enriched for FPs, likely due to a higher rate of nontargeted alternative alleles close to array-targeted P/LP variants. Conclusion: In AGHI, we have implemented an array-based process to screen for highly penetrant genetic variants in actionable disease genes. We demonstrate the need for clinical validation of array-identified variants in direct-to-consumer or population testing, especially for diverse populations.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Bowling KM; Thompson ML; Gray DE; Lawlor JMJ; Williams K; East KM; Kelley WV; Moss IP; Absher DM; Partridge EC
  • Start Page

  • 280
  • End Page

  • 288
  • Volume

  • 23
  • Issue

  • 2