The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework pr... more The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing developed in a prior expert consensus process. The anonymous online survey included responses to 3 (of 6 possible) different clinical scenarios that summarized the application of the core concepts. There was a binary (yes/no) question asking respondents whether they agreed the scenarios included the minimum necessary and critical educational concepts to allow an informed decision. Respondents then provided open-ended feedback on what concepts were missing or could be removed. At least one scenario was comple...
With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome ed... more With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for HumanGenetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappr...
The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System cou... more The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery.
Additional file 1: Supplementary Methods. Detailed description of methods for operationalizing th... more Additional file 1: Supplementary Methods. Detailed description of methods for operationalizing the CADRe pre- and post-test rubrics.
Purpose: Informed consent for genetic testing has historically been acquired during pretest genet... more Purpose: Informed consent for genetic testing has historically been acquired during pretest genetic counseling, without specific guidance defining which core concepts are required. Methods: The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendations Workgroup (CADRe) used an expert consensus process to identify the core concepts essential to consent for clinical genetic testing. A literature review identified 77 concepts that are included in informed consent for genetic tests. Twenty-five experts (9 medical geneticists, 8 genetic counselors, and 9 bioethicists) completed two rounds of surveys ranking concepts’ importance to informed consent. Results: The most highly ranked concepts included: (1) genetic testing is voluntary; (2) why is the test recommended and what does it test for?; (3) what results will be returned and to whom?; (4) are there other types of potential results, and what choices exist?; (5) how will the prognosis and management be impacted by result...
Genetics in medicine : official journal of the American College of Medical Genetics, Jan 6, 2018
In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Di... more In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Disclosure Recommendations (CADRe) Workgroup of the Clinical Genome Resource (ClinGen; clinicalgenome.org ) developed guidance to facilitate communication about genetic testing and efficiently improve the patient experience. Considering ethical, legal, and social implications, and medical factors, CADRe developed and pilot tested two rubrics addressing consent for genetic testing and results disclosure. The CADRe rubrics allow for adjusting the communication approach based on circumstances specific to patients and ordering clinicians. We present results of a formative survey of 66 genetics clinicians to assess the consent rubric for nine genes (MLH1, CDH1, TP53, GJB2, OTC; DMD, HTT, and CYP2C9/VKORC1). We also conducted interviews and focus groups with family and patient stakeholders (N = 18), nongenetics specialists (N = 27), and genetics clinicians (N = 32) on both rubrics. Formative eva...
ABSTRACTBackgroundResearch cohorts with linked genomic data exist, or are being developed, at man... more ABSTRACTBackgroundResearch cohorts with linked genomic data exist, or are being developed, at many research centers. Within any such “sequenced cohort” of more than 100 participants, it is likely that there are participants with previously undisclosed risk for life-threatening monogenic diseases that could be identified with targeted analysis of their existing data. Identification of such disease-associated findings are not usually primary to the enrollment research goals. At Geisinger Health System, MyCode® Community Health Initiative (MyCode) participants represent one such large sequenced cohort. Since 2013, MyCode participants in discovery research have been consented for secondary analysis of their existing research genomic sequences to allow delivery of medically actionable findings to them and their healthcare providers. This return of genomic results program was developed to manage an anticipated 3.5% of MyCode participants who will receive clinically confirmed genomic varia...
Copy number variants (CNVs) are a substantial source of genomic variation and contribute to a wid... more Copy number variants (CNVs) are a substantial source of genomic variation and contribute to a wide range of human disorders. Gene-disrupting exonic CNVs have important clinical implications as they can underlie variability in disease presentation and susceptibility. The relationship between exonic CNVs and clinical traits has not been broadly explored at the population level, primarily due to technical challenges. We surveyed common and rare CNVs in the exome sequences of 50,726 adult DiscovEHR study participants with linked electronic health records (EHRs). We evaluated the diagnostic yield and clinical expressivity of known pathogenic CNVs, and performed tests of association with EHR-derived serum lipids, thereby evaluating the relationship between CNVs and complex traits and phenotypes in an unbiased, real-world clinical context. We identified CNVs from megabase to exon-level resolution, demonstrating reliable, high-throughput detection of clinically relevant exonic CNVs. In doin...
Laboratory regulations provide rules to establish consistency and to evaluate performance. They a... more Laboratory regulations provide rules to establish consistency and to evaluate performance. They also set out the qualifications and experience needed for laboratory staff to fulfill regulatory requirements and meet professional standards. Clinical genetic counselors play a significant role in determining which tests to offer patients, which laboratories to consider for testing, and which phenotypic information to provide to the clinical laboratory to improve the interpretation of test results. This chapter discusses laboratory regulations pertinent to the type of genetic testing offered and specimens received in the laboratory. The goal is to help the laboratory genetic counselor understand the regulatory oversight of genetic testing and the quality management of clinical laboratory operations.
Most disorders caused by copy number variants (CNVs) display significant clinical variability, of... more Most disorders caused by copy number variants (CNVs) display significant clinical variability, often referred to as incomplete penetrance and variable expressivity. Genetic and environmental sources of this variability are not well understood. To investigate the contributors to phenotypic variability in probands with CNVs involving the same genomic region; to measure the effect size for de novo mutation events; and to explore the contribution of familial background to resulting cognitive, behavioral, and motor performance outcomes in probands with de novo CNVs. Family-based study design with a volunteer sample of 56 individuals with de novo 16p11.2 deletions and their noncarrier parents and siblings from the Simons Variation in Individuals Project. We used linear mixed-model analysis to measure effect size and intraclass correlation to determine the influence of family background for a de novo CNV on quantitative traits representing the following 3 neurodevelopmental domains: cognit...
Additional file 2: Supplementary Table S1. All CADRe communication recommendations for the standa... more Additional file 2: Supplementary Table S1. All CADRe communication recommendations for the standard testing indications.
JAAPA : official journal of the American Academy of Physician Assistants, 2008
... Joseph D. McInerney, MA, MS, is executive director, National Coalition for Health Professiona... more ... Joseph D. McInerney, MA, MS, is executive director, National Coalition for Health Professional Education in Genetics, Lutherville, Maryland. W. Andrew Faucett, MS, CGC, is an instructor at Emory University School of Medicine, Atlanta, Georgia. PAs and the practice of ...
The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework pr... more The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing developed in a prior expert consensus process. The anonymous online survey included responses to 3 (of 6 possible) different clinical scenarios that summarized the application of the core concepts. There was a binary (yes/no) question asking respondents whether they agreed the scenarios included the minimum necessary and critical educational concepts to allow an informed decision. Respondents then provided open-ended feedback on what concepts were missing or could be removed. At least one scenario was comple...
With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome ed... more With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for HumanGenetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappr...
The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System cou... more The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery.
Additional file 1: Supplementary Methods. Detailed description of methods for operationalizing th... more Additional file 1: Supplementary Methods. Detailed description of methods for operationalizing the CADRe pre- and post-test rubrics.
Purpose: Informed consent for genetic testing has historically been acquired during pretest genet... more Purpose: Informed consent for genetic testing has historically been acquired during pretest genetic counseling, without specific guidance defining which core concepts are required. Methods: The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendations Workgroup (CADRe) used an expert consensus process to identify the core concepts essential to consent for clinical genetic testing. A literature review identified 77 concepts that are included in informed consent for genetic tests. Twenty-five experts (9 medical geneticists, 8 genetic counselors, and 9 bioethicists) completed two rounds of surveys ranking concepts’ importance to informed consent. Results: The most highly ranked concepts included: (1) genetic testing is voluntary; (2) why is the test recommended and what does it test for?; (3) what results will be returned and to whom?; (4) are there other types of potential results, and what choices exist?; (5) how will the prognosis and management be impacted by result...
Genetics in medicine : official journal of the American College of Medical Genetics, Jan 6, 2018
In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Di... more In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Disclosure Recommendations (CADRe) Workgroup of the Clinical Genome Resource (ClinGen; clinicalgenome.org ) developed guidance to facilitate communication about genetic testing and efficiently improve the patient experience. Considering ethical, legal, and social implications, and medical factors, CADRe developed and pilot tested two rubrics addressing consent for genetic testing and results disclosure. The CADRe rubrics allow for adjusting the communication approach based on circumstances specific to patients and ordering clinicians. We present results of a formative survey of 66 genetics clinicians to assess the consent rubric for nine genes (MLH1, CDH1, TP53, GJB2, OTC; DMD, HTT, and CYP2C9/VKORC1). We also conducted interviews and focus groups with family and patient stakeholders (N = 18), nongenetics specialists (N = 27), and genetics clinicians (N = 32) on both rubrics. Formative eva...
ABSTRACTBackgroundResearch cohorts with linked genomic data exist, or are being developed, at man... more ABSTRACTBackgroundResearch cohorts with linked genomic data exist, or are being developed, at many research centers. Within any such “sequenced cohort” of more than 100 participants, it is likely that there are participants with previously undisclosed risk for life-threatening monogenic diseases that could be identified with targeted analysis of their existing data. Identification of such disease-associated findings are not usually primary to the enrollment research goals. At Geisinger Health System, MyCode® Community Health Initiative (MyCode) participants represent one such large sequenced cohort. Since 2013, MyCode participants in discovery research have been consented for secondary analysis of their existing research genomic sequences to allow delivery of medically actionable findings to them and their healthcare providers. This return of genomic results program was developed to manage an anticipated 3.5% of MyCode participants who will receive clinically confirmed genomic varia...
Copy number variants (CNVs) are a substantial source of genomic variation and contribute to a wid... more Copy number variants (CNVs) are a substantial source of genomic variation and contribute to a wide range of human disorders. Gene-disrupting exonic CNVs have important clinical implications as they can underlie variability in disease presentation and susceptibility. The relationship between exonic CNVs and clinical traits has not been broadly explored at the population level, primarily due to technical challenges. We surveyed common and rare CNVs in the exome sequences of 50,726 adult DiscovEHR study participants with linked electronic health records (EHRs). We evaluated the diagnostic yield and clinical expressivity of known pathogenic CNVs, and performed tests of association with EHR-derived serum lipids, thereby evaluating the relationship between CNVs and complex traits and phenotypes in an unbiased, real-world clinical context. We identified CNVs from megabase to exon-level resolution, demonstrating reliable, high-throughput detection of clinically relevant exonic CNVs. In doin...
Laboratory regulations provide rules to establish consistency and to evaluate performance. They a... more Laboratory regulations provide rules to establish consistency and to evaluate performance. They also set out the qualifications and experience needed for laboratory staff to fulfill regulatory requirements and meet professional standards. Clinical genetic counselors play a significant role in determining which tests to offer patients, which laboratories to consider for testing, and which phenotypic information to provide to the clinical laboratory to improve the interpretation of test results. This chapter discusses laboratory regulations pertinent to the type of genetic testing offered and specimens received in the laboratory. The goal is to help the laboratory genetic counselor understand the regulatory oversight of genetic testing and the quality management of clinical laboratory operations.
Most disorders caused by copy number variants (CNVs) display significant clinical variability, of... more Most disorders caused by copy number variants (CNVs) display significant clinical variability, often referred to as incomplete penetrance and variable expressivity. Genetic and environmental sources of this variability are not well understood. To investigate the contributors to phenotypic variability in probands with CNVs involving the same genomic region; to measure the effect size for de novo mutation events; and to explore the contribution of familial background to resulting cognitive, behavioral, and motor performance outcomes in probands with de novo CNVs. Family-based study design with a volunteer sample of 56 individuals with de novo 16p11.2 deletions and their noncarrier parents and siblings from the Simons Variation in Individuals Project. We used linear mixed-model analysis to measure effect size and intraclass correlation to determine the influence of family background for a de novo CNV on quantitative traits representing the following 3 neurodevelopmental domains: cognit...
Additional file 2: Supplementary Table S1. All CADRe communication recommendations for the standa... more Additional file 2: Supplementary Table S1. All CADRe communication recommendations for the standard testing indications.
JAAPA : official journal of the American Academy of Physician Assistants, 2008
... Joseph D. McInerney, MA, MS, is executive director, National Coalition for Health Professiona... more ... Joseph D. McInerney, MA, MS, is executive director, National Coalition for Health Professional Education in Genetics, Lutherville, Maryland. W. Andrew Faucett, MS, CGC, is an instructor at Emory University School of Medicine, Atlanta, Georgia. PAs and the practice of ...
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