Kristin A. Maloney

An openly available online tool for implementing the ACMG/AMP standards and guidelines for the interpretation of sequence variants.

An openly available online tool for implementing the ACMG/AMP standards and guidelines for the interpretation of sequence variants

Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry.

To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVars correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=−0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations.

Educational innovations in clinical pharmacogenomics

Genetic and genomic discovery is revolutionizing medicine at an extraordinary pace, leading to a better understanding of disease and improved treatments for patients. This advanced pace of discovery presents an urgency to expand medical school curricula to include genetic and genomic testing (including pharmacogenomics), and integration of genomic medicine into clinical practice. Consequently, organizations and healthcare authorities have charged medical schools with training future physicians to be competent in their knowledge of genomic implementation.

Prioritizing Approaches to Engage Community Members and Build Trust in Biobanks: A Survey of Attitudes and Opinions of Adults within Outpatient Practices at the University of Maryland

Background: Achieving high participation of communities representative of all sub-populations is needed in order to ensure broad applicability of biobank study findings. This study aimed to understand potentially mutable attitudes and opinions commonly correlated with biobank participation in order to inform approaches to promote participation in biobanks. Methods: Adults from two University of Maryland (UMD) Faculty Physicians, Inc. outpatient practices were invited to watch a video and complete a survey about a new biobank initiative. We used: Chi-square to assess the relationship between willingness to join the biobank and participant characteristics, other potentially mutable attitudes and opinions, and trust in the UMD. We also used t-test to assess the relationship with trust in medical research. We also prioritize proposed actions to improve attitudes and opinions about joining biobanks according to perceived responsiveness. Results: 169 participants completed the study, 51% of whom indicated a willingness to join the biobank. Willingness to join the biobank was not associated with age, gender, race, or education but was associated with respondent comfort sharing samples and clinical information, concerns related to confidentiality, potential for misuse of information, trust in UMD, and perceived health benefit. In ranked order, potential actions we surveyed that might alleviate some of these concerns include: increase chances to learn more about the biobank, increase opportunities to be updated, striving to put community concerns first, including involving community members as leaders of biobank research, and involving community members in decision making. Conclusions: This study identified several attitudes and opinions that influence decisions to join a biobank, including many concerns that could potentially be addressed by engaging community members. We also demonstrate our method of prioritizing ways to improve attitudes and opinions about joining a biobank according to perceived responsiveness.

Genetic Counseling for Diabetes Mellitus

Most diabetes is polygenic in etiology, with (type 1 diabetes, T1DM) or without (type 2 diabetes, T2DM) an autoimmune basis. Genetic counseling for diabetes generally focuses on providing empiric risk information based on family history and/or the effects of maternal hyperglycemia on pregnancy outcome. An estimated one to five percent of diabetes is monogenic in nature, e.g., maturity onset diabetes of the young, with molecular testing and etiology-based treatment available. However, recent studies show that most monogenic diabetes is misdiagnosed as T1DM or T2DM. While efforts are underway to increase the rate of diagnosis in the diabetes clinic, genetic counselors and clinical geneticists are in a prime position to identify monogenic cases through targeted questions during a family history combined with working in conjunction with diabetes professionals to diagnose and assure proper treatment and familial risk assessment for individuals with monogenic diabetes.

Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype‐Guided Antiplatelet Therapy

CYP2C19 genotype‐guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions.

Parkinson’s Disease: Patients’ Knowledge, Attitudes, and Interest in Genetic Counseling

The objective of this study was to assess the genetics knowledge of patients with Parkinson’s disease (PD), and to explore their attitudes on genetic testing and interest in genetic counseling. We surveyed 158 patients from the University of Maryland Parkinson’s Disease and Movement Disorders Center. Patients averaged a score of 63% on general genetics knowledge and 73% on PD genetics knowledge. Participants had an overall positive attitude toward genetic testing: 80% believed that the use of genetic tests among people should be promoted, and 83% would undertake genetic test for PD if it was available. Patients reported a high interest to discuss the benefits, risks, and impacts of genetic testing for PD (mean sum score = 26, range = 9–35), and 43% patients expressed interest in meeting with a genetic counselor. Multivariate regression analysis showed that patients who had more positive attitudes toward genetic testing for PD were more interested in meeting with a genetic counselor (β = 0.6, p < 0.001). This study is the first to demonstrate an interest in genetic counseling among patients with PD. Our findings demonstrate a new niche for genetic counselors to support patients in clarifying gaps or misconceptions in knowledge about PD genetics as well as the possible risks, benefits, and limitations of genetic testing.

Genetic Counselors’ Experience with and Opinions on the Management of Newborn Screening Incidental Carrier Findings

Newborn screening (NBS) is a public health program whose aim is to identify infants who will be clinically affected with a serious metabolic, genetic, or endocrine disorder; however, the technology utilized by many NBS programs also detects infants who are heterozygous carriers for autosomal recessive conditions. Discussion surrounding disclosure of these incidental carrier findings remains controversial. The purpose of this study was to assess genetic counselors’ attitudes about disclosure of carrier status results generated by NBS and to gather data on their experiences with incidental carrier findings. An electronic survey was distributed to genetic counselors of all specialties via the NSGC listserv, and a total of 235 survey responses were analyzed. Quantitative data were analyzed using IBM SPSS v24, and qualitative data were manually analyzed for thematic analysis. Results show that the counselor participants were overall in favor of routine disclosure. Those with experience in NBS were much more likely to strongly agree with one or more reasons for disclosure (p < 0.001), whereas those with five or fewer years of experience were more likely to strongly agree with one or more reasons for non-disclosure (p = 0.031). Qualitative analysis identified key motivating factors for disclosure, including helping parents to understand a positive screen, parents may otherwise be unaware of reproductive risk and they may not otherwise have access to this information, and, while genetic testing is inherently a complex and ambiguous process, this does not justify non-disclosure. The main motivating factor for non-disclosure was the need for better counseling and informed consent. The data suggest that implementation of an “opt-in/out” policy for parents to decide whether or not to receive incidental findings would be beneficial. The results of this study support the continued disclosure of incidental carrier findings; however, additional research is necessary to further determine and implement the most effective disclosure practices.

Patient Care Situations Benefiting from Pharmacogenomic Testing

Purpose of ReviewPharmacogenomics is an evolving area in precision medicine that aims to identify patients who have variable drug response, detect those at risk for developing adverse events, and guide drug dosing. Guidelines for optimization of PGx testing are available for a number of drug-gene pairs, and evidence supporting the clinical utility of this service is growing in specific patient contexts. This report reviews a variety of patient care situations in which evidence is emerging to show patient benefit from pharmacogenomic (PGx) testing.Recent FindingsPreemptive PGx testing minimizes delays in treatment, reducing costs and time to therapeutic effect; however, preemptive testing is currently not feasible in all healthcare settings. Therefore, specific patient care situations that could benefit from PGx testing to be prioritized include medications requiring PGx testing, adverse drug reactions, therapeutic failures, polypharmacy, special populations, and specialty care settings such as cardiology, oncology, and psychiatry.SummaryAlthough preemptive PGx testing is likely the best option for patient care, implementation challenges are impeding its uptake. PGx testing is beneficial and more feasible in certain patient situations and may be a starting point for implementation of PGx testing in a care setting. Continued efforts to evaluate patient and provider use and outcomes of PGx testing services will be helpful in informing the current evidence base and standard of care.