Journal Article

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

Rehm, Heidi L., Linder, Jodell E., Rasmussen-Torvik, Laura J., Larson, Eric B., Jarvik, Gail P., Funke, Birgit H., Muzny, Donna M., Stanaway, Ian B., Rosenthal, Elisabeth A., Williams, Marc S., Chisholm, Rex L., Van Driest, Sara L., Leppig, Kathleen A., Roden, Dan M., Hakonarson, Hakon, Chung, Wendy K., Smith, Maureen E., Gordon, Adam S., Eng, Christine M., Amendola, Laura M., Venner, Eric, Gibbs, Richard A., Lennon, Niall J., Denny, Joshua C., Prows, Cynthia A., Wiesner, Georgia L., Crosslin, David R., Zouk, Hana, Walker, Kimberly, Witkowski, Leora, Fedotov, Alexander, Rasouly, Hila Milo, Leduc, Magalie S., Carrell, David S., Kullo, Iftikhar J.

2020

Overview

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.

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: Biomedical and Life Sciences / Biomedicine / Consent / Disease / Electronic health records / Exome / Genes / Genetic Testing / Genetics / Genome, Human - genetics / Genomes / Genomics / Health care / Human Genetics / Humans / Incidental Findings / Laboratory Medicine / Medical records / Neoplasms - genetics / Working groups