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.
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).
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.
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.
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The eMERGE Phase III Network was initiated and funded by NHGRI through the following grants: U01HG8657 (Kaiser Permanente Washington/University of Washington); U01HG8685 (Brigham and Women’s Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children’s Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children’s Hospital of Philadelphia); U01HG8673 (Northwestern University); MD007593 (Meharry Medical College); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare/Broad Institute); and U01HG8664 (Baylor College of Medicine).
All data sets summarized here will be publicly available in the dbGaP repository under phs001616.v1.p1 and pre-dbGaP submission access can also be requested on the eMERGE website https://emerge-network.org.
D.R.C. serves on a consulting board for UnitedHealth Group with precision medicine efforts, which is unrelated to this paper. C.M.E. is a full-time employee/faculty member of Baylor College of Medicine. Through a professional services agreement, she serves as Chief Medical Officer and Chief Quality Officer of Baylor Genetics. R.A.G. declares that Baylor College of Medicine receives payments from Baylor Genetics Laboratories, which provides services for genetic testing; Baylor College of Medicine is part owner of Codified Genomics. H.L.R. and H.Z. are employed at Massachusetts General Hospital, which receives royalties on sales of GeneInsight Software. E.V. is a cofounder of Codified Genomics. G.L.W. is a member of the External Advisory Panel for the ClinGen Clinical Genome Resource Project. The other authors declare no conflicts of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Gordon, A.S., Zouk, H., Venner, E. et al. Frequency of genomic secondary findings among 21,915 eMERGE network participants. Genet Med (2020). https://doi.org/10.1038/s41436-020-0810-9
- personal genomics
- clinical sequencing
- incidental findings secondary findings