Disclaimer: These recommendations are designed primarily as an educational resource for medical geneticists and other healthcare providers to help them provide quality medical services. Adherence to ...these recommendations is completely voluntary and does not necessarily assure a successful medical outcome. These recommendations should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed toward obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this statement. Clinicians also are advised to take notice of the date this statement was adopted and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.
To promote standardized reporting of actionable information from clinical genomic sequencing, in 2013, the American College of Medical Genetics and Genomics (ACMG) published a minimum list of genes to be reported as incidental or secondary findings. The goal was to identify and manage risks for selected highly penetrant genetic disorders through established interventions aimed at preventing or significantly reducing morbidity and mortality. The ACMG subsequently established the Secondary Findings Maintenance Working Group to develop a process for curating and updating the list over time. We describe here the new process for accepting and evaluating nominations for updates to the secondary findings list. We also report outcomes from six nominations received in the initial 15 months after the process was implemented. Applying the new process while upholding the core principles of the original policy statement resulted in the addition of four genes and removal of one gene; one gene did not meet criteria for inclusion. The updated secondary findings minimum list includes 59 medically actionable genes recommended for return in clinical genomic sequencing. We discuss future areas of focus, encourage continued input from the medical community, and call for research on the impact of returning genomic secondary findings.
In clinical exome and genome sequencing, there is a potential for the recognition and reporting of incidental or secondary findings unrelated to the indication for ordering the sequencing but of ...medical value for patient care. The American College of Medical Genetics and Genomics (ACMG) recently published a policy statement on clinical sequencing that emphasized the importance of alerting the patient to the possibility of such results in pretest patient discussions, clinical testing, and reporting of results. The ACMG appointed a Working Group on Incidental Findings in Clinical Exome and Genome Sequencing to make recommendations about responsible management of incidental findings when patients undergo exome or genome sequencing. This Working Group conducted a year-long consensus process, including an open forum at the 2012 Annual Meeting and review by outside experts, and produced recommendations that have been approved by the ACMG Board. Specific and detailed recommendations, and the background and rationale for these recommendations, are described herein. The ACMG recommends that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here. This evaluation and reporting should be performed for all clinical germline (constitutional) exome and genome sequencing, including the "normal" of tumor-normal subtractive analyses in all subjects, irrespective of age but excluding fetal samples. We recognize that there are insufficient data on penetrance and clinical utility to fully support these recommendations, and we encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.
Purpose Significant concerns exist regarding the potential for unwarranted behavior changes and the overuse of health care resources in response to direct-to-consumer personal genomic testing (PGT). ...However, little is known about customers' behaviors after PGT. Methods Longitudinal surveys were given to new customers of 23andMe (Mountain View, CA) and Pathway Genomics (San Diego, CA). Survey data were linked to individual-level PGT results through a secure data transfer process. Results Of the 1,042 customers who completed baseline and 6-month surveys (response rate, 71.2%), 762 had complete cancer-related data and were analyzed. Most customers reported that learning about their genetic risk of cancers was a motivation for testing (colorectal, 88%; prostate, 95%; breast, 94%). No customers tested positive for pathogenic mutations in highly penetrant cancer susceptibility genes. A minority of individuals received elevated single nucleotide polymorphism-based PGT cancer risk estimates (colorectal, 24%; prostate, 24%; breast, 12%). At 6 months, customers who received elevated PGT cancer risk estimates were not significantly more likely to change their diet, exercise, or advanced planning behaviors or engage in cancer screening, compared with individuals at average or reduced risk. Men who received elevated PGT prostate cancer risk estimates changed their vitamin and supplement use more than those at average or reduced risk (22% v 7.6%, respectively; adjusted odds ratio, 3.41; 95% CI, 1.44 to 8.18). Predictors of 6-month behavior include baseline behavior (exercise, vitamin or supplement use, and screening), worse health status (diet and vitamin or supplement use), and older age (advanced planning, screening). Conclusion Most adults receiving elevated direct-to-consumer PGT single nucleotide polymorphism-based cancer risk estimates did not significantly change their diet, exercise, advanced care planning, or cancer screening behaviors.
The development of massively parallel sequencing (or next-generation sequencing) has facilitated a rapid implementation of genomic sequencing in clinical medicine. Genomic sequencing (GS) is now an ...essential tool for evaluating rare disorders, identifying therapeutic targets in neoplasms, and screening for prenatal aneuploidy. Emerging applications, such as GS for preconception carrier screening and predisposition screening in healthy individuals, are being explored in research settings and utilized by members of the public eager to incorporate genomic information into their health management. The rapid pace of adoption has created challenges for all stakeholders in clinical GS, from standardizing variant interpretation approaches in clinical molecular laboratories to ensuring that nongeneticist clinicians are prepared for new types of clinical information. Clinical GS faces a pivotal moment, as the vast potential of new quantities and types of data enable further clinical innovation and complicated implementation questions continue to be resolved.
Objective
To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions.
Methods
We performed a ...randomized controlled trial among first‐degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE‐RA) group received the web‐based PRE‐RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans‐theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk–related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post‐intervention. Subjects reported behavior change at each visit. We performed intent‐to‐treat analyses using generalized estimating equations for the binary outcome.
Results
Subjects randomized to PRE‐RA were more likely to increase ladder scores over post‐intervention assessments (relative risk 1.23, 95% confidence interval 95% CI 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE‐RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age‐adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE‐RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18).
Conclusion
Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk–related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes, such as RA‐related autoantibody production or RA development.
The American College of Medical Genetics and Genomics (ACMG) recommendations for reporting of incidental (now “secondary”) findings in clinical exome and genome sequencing (Green et al., Genet Med ...15:565, 2013) is an often cited and sometimes misapplied professional guideline. To best approach the current state of secondary findings (SFs) in genomic medicine, and consider their impact, it is helpful to understand how and why the guideline was created. Of particular importance is the context ‐ the state of the science and clinical practice during 2011–2012 when the guideline were initially developed. This paper will review the setting before the guidelines were published, and empiric research and discussion that has occurred since.
Polygenic scores (PGS) are primed for use in personalized risk assessments for common, complex conditions and population health screening. Although there is growing evidence supporting the clinical ...validity of these scores in certain diseases, presently, there is no consensus on best practices for constructing PGS or demonstrated clinical utility in practice. Despite these evidence gaps, individuals can access their PGS information through commercial entities, research programs, and clinical programs. This prompts the immediate need for educational resources for clinicians encountering PGS information in clinical practice. This practice resource is intended to increase genetic counselors' and other healthcare providers' understanding and comfort with PGS used in personalized risk assessments. Drawing on best practices in clinical genomics, we discuss the unique considerations for polygenic‐based (1) testing, (2) clinical genetic counseling, and (3) translation to population health services. This practice resource outlines the emerging uses of PGS, as well as the critical limitations of this technology that need to be addressed before wide‐scale implementation.
•This trial compared disclosure of chronic disease risk to a standard strategy.•Personalized risk disclosure lowered concern for developing chronic disease.•Disclosing personalized chronic disease ...risk may provide reassurance to those at risk.
To investigate the effect of providing comprehensive personalized risk information on concern for chronic disease development.
Unaffected first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients (n = 238) were randomly allocated to: 1) disclosure of RA risk personalized to demographics, genetics, biomarkers, and behaviors using a web-based tool (PRE-RA arm, n = 78); 2) PRE-RA with interpretation by a health educator (PRE-RA Plus arm, n = 80); and 3) standard RA education (Comparison arm, n = 80). Concern for developing RA was assessed at baseline and immediately, 6 weeks, 6 months, and 12 months post-intervention.
FDRs randomized to PRE-RA arms were less concerned about developing RA than the Comparison arm at all post-intervention assessments (p < 0.05). Among those concerned about RA risk at baseline, the PRE-RA (OR = 4.7, 95%CI 1.5–14.4) and PRE-RA Plus (OR = 5.2, 95%CI 1.6–17.3) arms were more likely to have reassurance 6 months post-intervention than the Comparison arm.
A comprehensive tool provided reassurance to those at risk for developing a chronic disease, with or without interpretation from a health educator, compared to standard education.
Individuals may be more likely to be reassured using a personalized chronic disease risk disclosure tool than a standard non-personalized approach.
We surveyed parents to ascertain interest in newborn genomic testing and determine whether these queries would provoke refusal of conventional state-mandated newborn screening.
After a brief genetics ...orientation, parents rated their interest in receiving genomic testing for their healthy newborn on a 5-point Likert scale and answered questions about demographics and health history. We used logistic regression to explore factors associated with interest in genomic testing and tracked any subsequent rejection of newborn screening.
We queried 514 parents within 48 hours after birth while still in hospital (mean age (SD) 32.7 (6.4) years, 65.2% female, 61.2% white, 79.3% married). Parents reported being not at all (6.4%), a little (10.9%), somewhat (36.6%), very (28.0%), or extremely (18.1%) interested in genomic testing for their newborns. None refused state-mandated newborn screening. Married participants and those with health concerns about their infant were less interested in newborn genomic testing (P = 0.012 and P = 0.030, respectively). Degree of interest for mothers and fathers was discordant (at least two categories different) for 24.4% of couples.
Interest in newborn genomic testing was high among parents of healthy newborns, and the majority of couples had similar levels of interest. Surveying parents about genomic sequencing did not prompt rejection of newborn screening.Genet Med 17 6, 501-504.
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