- Browse by Author
Browsing by Author "Judge, Daniel P."
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry(American Medical Association, 2023) Jordan, Elizabeth; Kinnamon, Daniel D.; Haas, Garrie J.; Hofmeyer, Mark; Kransdorf, Evan; Ewald, Gregory A.; Morris, Alanna A.; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Tang, W. H. Wilson; Garg, Sonia; Trachtenberg, Barry H.; Shah, Palak; Pamboukian, Salpy V.; Sweitzer, Nancy K.; Wheeler, Matthew T.; Wilcox, Jane E.; Katz, Stuart; Pan, Stephen; Jimenez, Javier; Fishbein, Daniel P.; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S.; Judge, Daniel P.; Moore, Charles K.; Mead, Jonathan O.; Hurst, Natalie; Cao, Jinwen; Huggins, Gordon S.; Cowan, Jason; Ni, Hanyu; Rehm, Heidi L.; Jarvik, Gail P.; Vatta, Matteo; Burke, Wylie; Hershberger, Ray E.; DCM Precision Medicine Study of the DCM Consortium; Medical and Molecular Genetics, School of MedicineImportance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main outcomes and measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.Item Genetic Evaluation of Cardiomyopathy - a Heart Failure Society of America Practice Guideline(Elsevier, 2018) Hershberger, Ray E.; Givertz, Michael; Ho, Carolyn Y.; Judge, Daniel P.; Kantor, Paul; McBride, Kim L.; Morales, Ana; Taylor, Matthew R. G.; Vatta, Matteo; Ware, Stephanie M.; Pediatrics, School of MedicineThis guideline describes the approach and expertise needed for the genetic evaluation of cardiomyopathy. First published in 2009 by the Heart Failure Society of America (HFSA), this guidance has now been updated in collaboration with the American College of Medical Genetics and Genomics (ACMG). The writing group, composed of cardiologists and genetics professionals with expertise in adult and pediatric cardiomyopathy, reflects the emergence and increased clinical activity devoted to cardiovascular genetic medicine. The genetic evaluation of cardiomyopathy is a rapidly emerging key clinical priority, as high throughput sequencing is now feasible for clinical testing, and conventional interventions can improve survival, reduce morbidity, and enhance quality of life. Moreover, specific interventions may be guided by genetic analysis. A systematic approach is recommended: always a comprehensive family history; an expert phenotypic evaluation of the proband and at-risk family members to confirm a diagnosis and guide genetic test selection and interpretation; referral to expert centers as needed; genetic testing, with pre- and post-test genetic counseling; and specific guidance as indicated for drug and device therapies. The evaluation of infants and children demands special expertise. The approach to manage secondary and incidental sequence findings as recommended by the ACMG is provided.