Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications

Murdock, David R.; Metcalf, Ginger; Murugan, Mullai; Hadley, Trevor; Chander, Varuna; Vries, Paul S. de; Jia, Xiaoming; Hussain, Aliza; Agha, Ali; Sabo, Aniko; Li, Shoudong; Meng, Qingchang; Hu, Jianhong; Tian, Xia; Cohen, Mark H.; Yi, Victoria; Kovar, Christie; Gingras, Marie Claude; Korchina, Viktoriya; Howard, Chad; Riconda, Daniel; Pereira, Stacey; Smith, Hadley Stevens; Huda, Z; Buentello, Alexandria; Marino, Patricia; Leiber, Lee; Balasubramanyam, Ashok; Amos, Christopher I.; Civitello, Andrew B.; Chelu, Mihail G.; Maag, Ronald; McGuire, Amy L.; Boerwinkle, Eric; Wehrens, Xander H.T.; Ballantyne, Christie M.; Gibbs, Richard A.

doi:10.1038/s41436-021-01294-8

Cited by 21 publications

(18 citation statements)

References 48 publications

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“…Similar algorithms have been clinically validated for risk assessment in other common and complex genetic disorders, such as cardiovascular disease. 16 , 17 …”

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confidence: 99%

Genome Sequencing in the Parkinson Disease Clinic

et al. 2022

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Background and ObjectivesGenetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics.MethodsIn 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Based on the results, 231 patients (age = 67 years, 63% male) were surveyed on interest in genetic testing and responses to vignettes covering (1) familial risk of PD (LRRK2); (2) risk of PD dementia (GBA); (3) PD genetic risk score; and (4) secondary, medically actionable variants (BRCA1).ResultsGenome sequencing revealed a LRRK2 variant in 3% and a GBA risk variant in 10% of our clinical sample. The genetic risk score was normally distributed, identifying 41 subjects with a high risk of PD. Medically actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded that they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with a potential risk for dementia or medically actionable findings, and most (75%) expressed interest in learning their PD genetic risk score.DiscussionOur results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.

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“…Similar algorithms have been clinically validated for risk assessment in other common and complex genetic disorders, such as cardiovascular disease. 16 , 17 …”

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confidence: 99%

Genome Sequencing in the Parkinson Disease Clinic

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“…This lack of routine testing as part of care pathway creates a "diagnostic gap" (i.e., a delay in time from disease manifestation to establishing a definitive diagnosis) that can lead to inappropriate or ineffective treatment in patients suffering from inherited CVDs. In a recent study from Baylor College of Medicine's Human Genome Sequencing Center, 84% of surveyed physicians reported medical management changes, including specialist referrals, cardiac testing, and medication changes, after receiving the results of a panel of genes associated with CVDs [12].…”

Section: Genetic Testing Gap In Cardiovascular Diseasesmentioning

confidence: 99%

“…With advancements in genetic testing technologies, preemptive genetic testing for various cardiomyopathies may be useful in the presence of an asymptomatic type 1 Brugada ECG pattern, family history of dilated cardiomyopathy, or the development of spontaneous coronary artery dissection (SCAD). While a recent study by Murdock and colleagues demonstrated the diagnostic potential of genetics guided coronary artery disease (CAD) risk factor management based on LPA polymorphisms and polygenic risk, genetic testing for a selection of well-understood variant-phenotype associations remains very limited (i.e., a "treatment gap") [12]. With further research and development, comprehensive genetic testing could become routinely used in clinical cardiovascular practice and applied to primary disease prevention and the facilitation of precision cardiovascular medicine.…”

Section: Genetic Testing Gap In Cardiovascular Diseasesmentioning

confidence: 99%

Artificial Intelligence and Cardiovascular Genetics

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et al. 2022

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Polygenic diseases, which are genetic disorders caused by the combined action of multiple genes, pose unique and significant challenges for the diagnosis and management of affected patients. A major goal of cardiovascular medicine has been to understand how genetic variation leads to the clinical heterogeneity seen in polygenic cardiovascular diseases (CVDs). Recent advances and emerging technologies in artificial intelligence (AI), coupled with the ever-increasing availability of next generation sequencing (NGS) technologies, now provide researchers with unprecedented possibilities for dynamic and complex biological genomic analyses. Combining these technologies may lead to a deeper understanding of heterogeneous polygenic CVDs, better prognostic guidance, and, ultimately, greater personalized medicine. Advances will likely be achieved through increasingly frequent and robust genomic characterization of patients, as well the integration of genomic data with other clinical data, such as cardiac imaging, coronary angiography, and clinical biomarkers. This review discusses the current opportunities and limitations of genomics; provides a brief overview of AI; and identifies the current applications, limitations, and future directions of AI in genomics.

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“…In another study, Murdock et al [ 33 ] assessed the utility of sequencing 158 highly penetrant cardiovascular disease genes in 709 patients in an ambulatory cardiology clinic. This study offered the following important insights: 1) most patients (81%) pursued genetic testing when offered; 2) 64 patients (9%) were diagnosed with a Mendelian disease and only 2% of the cohort reported family history of cardiovascular disease; 3) the diagnostic yield was higher (13% hereditary cardiomyopathy and 12% aortopathy) in patients who reported family history of related diseases; and 4) surveyed cardiologists (n = 13) recommended changes to medical management for 84% of patients, including 72% who already had a clinical diagnosis [ 33 ]. It is possible that genetic diagnoses were missed because genetic testing is not routinely offered in clinical practice and/or that some patients with HTAD and other Mendelian cardiovascular diseases did not satisfy clinical criteria for testing.…”

Section: Genomic-guided Risk Stratification For Admentioning

confidence: 99%

“…HTAD is underdiagnosed and, if untreated, leads to fatal outcomes [ 25 , 32 , 33 ]. The feasibility and effectiveness of genomic testing and family health history assessment in different patient populations at risk for AD (eg, meet clinical genetic testing criteria v. all patients with AD) is not known and should be investigated prospectively.…”

Section: Clinical Utility and Access To Genomic Medicine Servicesmentioning

confidence: 99%