Abstract
BackgroundIncreasingly, genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. The latter is a particularly pernicious problem due to the historical lack of inclusion of racially and ethnically diverse populations in genomic research and genomic medicine. A further challenge is the rapidly changing landscape of genetic tests and considerations of cost, interpretation, and diagnostic yield for emerging modalities like whole-genome sequencing.MethodsThe NYCKidSeq project is a randomized controlled trial recruiting 1130 children and young adults predominantly from Harlem and the Bronx with suspected genetic disorders in three disease categories: neurologic, cardiovascular, and immunologic. Two clinical genetic tests will be performed for each participant, either proband, duo, or trio whole-genome sequencing (depending on sample availability) and proband targeted gene panels. Clinical utility, cost, and diagnostic yield of both testing modalities will be assessed. This study will evaluate the use of a novel, digital platform (GUÍA) to digitize the return of genomic results experience and improve participant understanding for English- and Spanish-speaking families. Surveys will collect data at three study visits: baseline (0 months), result disclosure visit (ROR1, + 3 months), and follow-up visit (ROR2, + 9 months). Outcomes will assess parental understanding of and attitudes toward receiving genomic results for their child and behavioral, psychological, and social impact of results. We will also conduct a pilot study to assess a digital tool called GenomeDiver designed to enhance communication between clinicians and genetic testing labs. We will evaluate GenomeDiver’s ability to increase the diagnostic yield compared to standard practices, improve clinician’s ability to perform targeted reverse phenotyping, and increase the efficiency of genetic testing lab personnel.DiscussionThe NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations. This work will inform strategies for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound.Trial registrationClinicalTrials.govNCT03738098. Registered on November 13, 2018Trial Sponsor: Icahn School of Medicine at Mount SinaiContact Name: Eimear Kenny, PhD (Principal Investigator)Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029Email: eimear.kenny@mssm.edu
Highlights
Genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations
The NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations
Eligible children are suspected of having an undiagnosed genetic disorder in three disease categories: neurologic, cardiovascular, and immunologic
Summary
Genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. While the majority of clinical sequencing currently uses panels or exomes, there is an increasing number of pilot programs using more advanced genetic modalities, such as whole-genome sequencing (WGS), which has the potential to capture all classes of genetic variation in one analysis [2,3,4] These advancements in genomic sequencing and testing have sparked innovation in methods for scaling genomic medicine services across health systems. Non-European individuals are more likely to receive variants of uncertain significance or misclassified results, which has been demonstrated in the context of genetic testing for hypertrophic cardiomyopathy and hereditary cancer risks in understudied populations [10,11,12,13] Evidence suggests that this bias is likely to persist in the ongoing and upcoming efforts to sequence entire genomes.
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