Frequency of genomic secondary findings among 21,915 eMERGE network participants

Genet Med. 2020 Sep;22(9):1470-1477. doi: 10.1038/s41436-020-0810-9. Epub 2020 Jun 17.


Purpose: Discovering an incidental finding (IF) or secondary finding (SF) is a potential result of genomic testing, but few data exist describing types and frequencies of SFs likely to appear in broader clinical populations.

Methods: The Electronic Medical Records and Genomics Network Phase III (eMERGE III) developed a CLIA-compliant sequencing panel of 109 genes and 1551 variants of clinical relevance or research interest and deployed this panel at ten clinical sites. We evaluated medically actionable SFs across 67 genes and 14 single-nucleotide variants (SNVs) in a diverse cohort of 21,915 participants drawn from a variety of settings (e.g., primary care, biobanks, specialty clinics).

Results: Correcting for testing indication, we found a 3.02% overall frequency of SFs; 2.54% from 59 genes the American College of Medical Genetics and Genomics recommends for SF return, and 0.48% in other genes, primarily HFE and PALB2. SFs associated with cancer susceptibility were most frequent (1.38%), followed by cardiovascular diseases (0.87%), and lipid disorders (0.50%). After removing HFE, the frequency of SFs and proportion of pathogenic versus likely pathogenic SFs did not differ in those self-identifying as White versus others.

Conclusion: Here we present frequencies and types of medically actionable secondary findings to support informed decision making by patients, participants, and practitioners engaged in genomic medicine.

Keywords: clinical sequencing; eMERGE; incidental findings secondary findings; personal genomics.