Circulation: Genomic and Precision Medicine最新文献

{"title":"Genome-Wide Association Study of Chronic Venous Insufficiency and Lymphedema in the Million Veteran Program.","authors":"Gina M Peloso, Nimish Adhikari, Melissa M Young, Kelly Cho, Scott Kinlay","doi":"10.1161/CIRCGEN.125.005442","DOIUrl":"10.1161/CIRCGEN.125.005442","url":null,"abstract":"<p><strong>Background: </strong>Lymphedema is a chronic condition characterized by the accumulation of fluid due to impaired lymphatic drainage, frequently occurring secondary to chronic venous insufficiency (CVI), malignancy, or obesity. Despite known environmental and clinical risk factors, the genetic contributors to lymphedema and CVI have been understudied.</p><p><strong>Methods: </strong>We conducted a multipopulation genome-wide association study in participants of the Million Veteran Program without cancer to identify genetic variants associated with CVI, lymphedema, and their cooccurrence. Individuals were categorized into 3 case groups: CVI only (n=34 664), lymphedema only (n=2452), and lymphedema+CVI (n=3283) and were compared with 367 684 controls.</p><p><strong>Results: </strong>We identified 11 genome-wide significant variants (<i>P</i><5×10^-8) in the multipopulation analysis, including 8 for CVI only, 1 for lymphedema only, and 2 for lymphedema+CVI, and 2 population-specific genetic variants. Three independent variants replicated in the UK Biobank for CVI only near <i>CASZ1</i>, <i>SLC12A2</i>, and <i>NDP</i>. Polygenic risk scores derived from the Million Veteran Program were associated with CVI in the UK Biobank and phenome-wide associations of CVI-associated variants revealed pleiotropic associations with cardiometabolic traits.</p><p><strong>Conclusions: </strong>These findings enhance our understanding of the genetic architecture of lymphatic dysfunction.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005442"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Whole-Genome Sequencing for Prediction of Venous Thromboembolism in Patients With Metastasized Solid Cancer.","authors":"Frits I Mulder, Noori A M Guman, Job van Riet, Roos J van Geffen, Thijs F van Haaps, Vahram Hovsepjan, Hanneke W M van Laarhoven, Geert A Cirkel, Filip Y F L de Vos, Hans M Westgeest, Laurens V Beerepoot, Judith de Vos-Geelen, Mariette Labots, Paul Hamberg, Annelie J E Vulink, Maartje Los, Aeilko H Zwinderman, Debbie G J Robbrecht, Maja J A de Jonge, Harry R Büller, Pieter W Kamphuisen, Bart Ferwerda, Neeltje Steeghs, Nick van Es","doi":"10.1161/CIRCGEN.124.005182","DOIUrl":"10.1161/CIRCGEN.124.005182","url":null,"abstract":"<p><strong>Background: </strong>International guidelines suggest prophylactic anticoagulation for patients with cancer at high risk of venous thromboembolism (VTE). Here, we evaluated whether tumor whole-genome sequencing data may improve the selection of high-risk patients.</p><p><strong>Methods: </strong>In a pan-cancer cohort of 3087 patients, associations of candidate clinical predictors, the germline extended 297-single nucleotide polymorphism polygenic risk score, tumor mutational characteristics, and somatic tumor mutations with VTE were estimated by calculating hazard ratios (HRs).</p><p><strong>Results: </strong>During 12-month follow-up, 237 (7.7%) developed VTE. The germline extended 297-single nucleotide polymorphism score was associated with VTE (HR per point increase, 2.11 [95% CI, 1.45-3.06]), as well as the total number of somatic structural variants (HR per 1000 increase, 1.21 [95% CI, 1.07-1.37]) and 129 somatic mutations (unadjusted <i>P</i><0.05), including <i>POLR2E</i> (HR, 3.34 [95% CI, 1.68-6.97]), <i>PALM</i> (HR, 3.73 [95% CI, 1.74-7.99]), <i>TBX22</i> (T-box Transcription Factor 22; HR, 2.47 [95% CI, 1.40-4.35]), and <i>ELANE</i> (HR, 3.22 [95% CI, 1.51-6.87]). To further explore the potential of tumor whole-genome sequencing, prediction models were constructed including selected clinical predictors only (model 1), clinical predictors and germline variants (model 2), and the combination of clinical predictors, germline variants, and 14 top discriminating somatic mutations (model 3). The optimism corrected concordance index was 0.66 (95% CI, 0.62-0.69) for model 1, 0.67 (95% CI, 0.62-0.72) for model 2, and 0.77 (95% CI, 0.72-0.81) for model 3. This was significantly higher than that of the currently endorsed clinical Khorana VTE risk score (concordance index, 0.55 [95% CI, 0.51-0.59]; <i>P</i><0.005).</p><p><strong>Conclusions: </strong>These data indicate that tumor whole-genome sequencing may improve VTE prediction by clinical risk scores. Validation studies to confirm these findings are needed.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005182"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Integrated Monogenic and Polygenic Risk Assessment Tool for Coronary Artery Disease and Its Application in a Community-Based Health Care Biobank.","authors":"Jianfeng Xu, Zhuqing Shi, Sumeet A Khetarpal, Ashley J Mulford, Osama Siddiqui, Huy Tran, Jun Wei, Annabelle Ashworth, S Lilly Zheng, David Duggan, Brian T Helfand, Henry M Dunnenberger, Peter J Hulick, David J Davidson, Amit V Khera, Aniruddh P Patel, Alan R Sanders, Arman Qamar","doi":"10.1161/CIRCGEN.125.005494","DOIUrl":"10.1161/CIRCGEN.125.005494","url":null,"abstract":"<p><strong>Background: </strong>Current genetic testing for coronary artery disease (CAD) primarily targets monogenic variants in individuals with severe hypercholesterolemia. Whether supplementing monogenic testing with polygenic risk scores for CAD and Lp(a; lipoprotein[a]) levels [PRS_Lp(a)] improves identification of high-risk individuals in the general population remains understudied.</p><p><strong>Methods: </strong>A genetic probability for CAD (GenProb_CAD), incorporating monogenic pathogenic variants (PVs), polygenic risk scores for CAD, and PRS_Lp(a) was developed using Cox regression in 226 145 UK Biobank participants, validated in the remaining 226 145 UK Biobank participants, and applied to 20 477 participants of the Genomic Health Initiative, a community-based health care biobank. Predictive performance was evaluated and adjusted for clinical risk factors.</p><p><strong>Results: </strong>In the UK Biobank development cohort, PVs, polygenic risk scores for CAD and PRS_Lp(a) were each independently associated with CAD. In the UK Biobank validation cohort, GenProb_CAD outperformed PVs and the polygenic risk score in predicting CAD and reclassified risk among PV carriers. GenProb_CAD identified 16% of participants as high risk, 46-fold more than PV carriers (0.35%), with comparable observed CAD prevalence (15.60% versus 15.43%). Nearly 50% of CAD with high-risk GenProb_CAD were premature. GenProb_CAD also independently predicted incident CAD after adjusting for clinical risk factors. Importantly, high-risk individuals defined by GenProb_CAD showed consistently elevated CAD incidence across all low-density lipoprotein cholesterol strata. When UK Biobank-derived coefficients and cutoffs were applied in the Genomic Health Initiative, GenProb_CAD substantially outperformed the PV-only strategy, identifying 1966 high-risk participants (345 developed CAD), far exceeding the 20 PV carriers detected among those with low-density lipoprotein cholesterol ≥190 mg/dL (5 developed CAD). A universal genetic testing strategy using GenProb_CAD would hypothetically identify 20.75% of all incident CAD, 69-fold higher than current monogenic testing (0.3%). Results were generally consistent across ancestry populations, although the sample size of non-European participants was limited.</p><p><strong>Conclusions: </strong>GenProb_CAD, a novel integrated genetic risk tool combining monogenic PVs, polygenic risk scores for CAD, and PRS_Lp(a), improves identification of individuals at high genetic risk for CAD across diverse populations.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005494"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARγ Antagonism: Expanding the Therapeutic Armamentarium in Arrhythmogenic Cardiomyopathy.","authors":"Stephen P Chelko","doi":"10.1161/CIRCGEN.126.005800","DOIUrl":"10.1161/CIRCGEN.126.005800","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005800"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting and Mitigating Bias for Inclusive and Trustworthy Clinical Research: A Scientific Statement From the American Heart Association.","authors":"Judy Zhong, Salah Al-Zaiti, Derrick A Bennett, Synho Do, Mario F L Gaudino, Judy W Gichoya, Salma M A Musaad, Sanjiv M Narayan, Tolulope Sajobi, Yu Shen, Antonis A Armoundas","doi":"10.1161/HCG.0000000000000101","DOIUrl":"10.1161/HCG.0000000000000101","url":null,"abstract":"<p><p>Bias in clinical research affects not only the internal validity of studies but also the equitable distribution of health benefits derived from studies. Among the most impactful forms are selection bias, attrition bias, and algorithmic bias, each of which is capable of distorting participant representation, treatment effect estimates, and model performance across important subgroups. This scientific statement provides a reference for cardiovascular researchers and clinicians, integrating detection, correction, and prevention strategies to address these biases. Selection bias may be mitigated through approaches such as inverse probability weighting and adjustment for sociodemographic imbalances; attrition bias can be addressed using intention-to-treat analyses and multiple imputation for missing data that are missing at random; algorithmic bias requires fairness-aware modeling, diverse training data sets, and explainable artificial intelligence techniques. These 3 forms of bias are not exhaustive, but their careful management is essential to achieving scientific rigor, fairness, and real-world applicability, and requires multidisciplinary collaboration to embed equity and validity throughout the research lifecycle.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e000101"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scalable System-Wide CYP2C19 Pharmacogenomic Testing Reveals 38% Excess Incidence of Adverse Events in Metabolizers Receiving Inappropriate Prescriptions.","authors":"Natalie Telis, Douglas Stoller, Christopher N Chapman, C Anwar A Chahal, Daniel P Judge, Douglas A Olson, Joseph J Grzymski, Catherine Hajek, Teresa Kruisselbrink, Nicole L Washington, Elizabeth T Cirulli","doi":"10.1161/CIRCGEN.125.005363","DOIUrl":"10.1161/CIRCGEN.125.005363","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005363"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biobank-Scale Plasma Proteomics Identifies Novel Biomarkers in Hypertrophic Cardiomyopathy.","authors":"Jonathan H Chan, Christopher Grace, Mohsen Mazidi, Robert Clarke, Carolyn Y Ho, Stefan Neubauer, Christopher M Kramer, Hugh Watkins, Anuj Goel","doi":"10.1161/CIRCGEN.125.005325","DOIUrl":"10.1161/CIRCGEN.125.005325","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic cardiomyopathy (HCM) is characterized by substantial heterogeneity in both clinical phenotype and risk of adverse outcomes, including heart failure and sudden cardiac death. This highlights the need for robust biomarkers for risk stratification, and while previous studies have identified the role of select plasma proteins, comprehensive large-scale proteomic analyses have been limited in HCM.</p><p><strong>Methods: </strong>We performed a case-control analysis of 2922 plasma proteins in 49 588 UK Biobank participants (100 HCM cases) to identify proteins associated with HCM. External replication analyses were performed in the deCODE Genetics Icelandic study (51 cases/38 904 controls) and All of Us (546 cases/41 049 controls) data sets. Associations with adverse clinical outcomes and cardiac endophenotypes of disease severity were further identified, and causal relationships were evaluated using Mendelian randomization. Relative biomarker importance was also assessed by joint modeling via machine learning.</p><p><strong>Results: </strong>We identified novel associations of ANGPT2 (angiopoietin-2) and LTBP2 (latent transforming growth factor-beta binding protein 2) with HCM, with both also showing prognostic utility for heart failure-related outcomes in HCM cases. We also confirmed the associations of established biomarkers (eg, NT-proBNP [N-terminal pro-B-type natriuretic peptide], troponins I and T) with HCM cases, cardiac imaging markers of disease severity, and adverse outcomes. Mendelian randomization analyses supported a causal effect of HCM on increasing NT-proBNP and troponin T levels.</p><p><strong>Conclusions: </strong>This biobank-scale plasma proteomic study in HCM identified ANGPT2 and LTBP2 as novel HCM biomarkers with potential diagnostic and prognostic utility. These findings highlight the potential for plasma proteomics to improve risk prediction and provide insight into HCM pathobiology.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005325"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Genome Sequencing Shows Diagnostic Utility in Infants With Congenital Heart Defects.","authors":"Matthew D Durbin, Lindsey R Helvaty, Alyx Posorske, Samuel X Zhang, Manyan Huang, Ming Li, Daniel Abreu, Korre Fairman, Gabrielle C Geddes, Benjamin M Helm, Benjamin J Landis, Alexis McEntire, Dana K Mitchell, Stephanie M Ware","doi":"10.1161/CIRCGEN.125.005367","DOIUrl":"10.1161/CIRCGEN.125.005367","url":null,"abstract":"<p><strong>Background: </strong>Congenital heart disease (CHD) is the most common birth defect and a leading cause of infant mortality. CHD often has a genetic cause, and recent studies demonstrate the utility of genetic testing. In clinical practice, genetic testing continues to evolve, and the incorporation of rapid genome sequencing (rGS) in CHD is a recent development that requires evaluation. Although smaller studies demonstrate the value of rGS, they also highlight the burden of results interpretation.</p><p><strong>Methods: </strong>We analyzed genetic testing in CHD at 2 time points, in 2018 and from 2022 to 2023, across a change in clinical testing guidelines from chromosome microarray to rGS.</p><p><strong>Results: </strong>In an analysis of 421 hospitalized infants with CHD, genetic testing was performed in 77.7%, and the rate was consistent across time and in all patient subtypes analyzed. There was a significant shift in testing modalities, where in 2018, chromosome microarray was the most common test performed, with diagnostic results for CHD in 14.3%, whereas in 2022 to 2023, rGS was the most frequent test performed, with results diagnostic for CHD in 16.9%. In addition, rGS identified 44% more unique genetic diagnoses than chromosome microarray.</p><p><strong>Conclusions: </strong>This is the most extensive study to highlight the value of rGS in patients with CHD. These findings have important implications for CHD patient management.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005367"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamut of Patients Referred to Cardiology for Question of Clonal Hematopoiesis.","authors":"Ohad Oren, Peter Libby","doi":"10.1161/CIRCGEN.125.005544","DOIUrl":"10.1161/CIRCGEN.125.005544","url":null,"abstract":"<p><p>Clonal hematopoiesis encompasses diverse somatic mutations in hematopoietic cells, ranging from age-related expansions to mutations acquired after cytotoxic therapy, with implications for hematologic malignancy and cardiovascular disease. We characterize the spectrum of patients referred to cardiology for clonal hematopoiesis, including incidental detection during cytopenia or cancer predisposition workup, coexisting malignancy, and posttherapy surveillance. High-risk features, large clone size, multiple mutations, and specific driver genes interact with traditional cardiovascular risk factors to influence ischemic events. Contextualizing clonal hematopoiesis by detection setting, genotype, and clinical history informs individualized cardiovascular evaluation and risk mitigation, guiding mechanistically targeted preventive strategies and trial design.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005544"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yield of Postmortem Genetic Testing in Sudden Arrhythmic Death Syndrome: A Systematic Review and Meta-Analysis.","authors":"Emanuele Monda, Sabrina Montuoro, Lia Crotti, Cristina Basso, Martina Caiazza, Emanuele Bobbio, Camillo Autore, Elena Arbelo, Gaetano Diana, Perry Mark Elliott, Eloisa Arbustini, Giuseppe Limongelli","doi":"10.1161/CIRCGEN.125.005523","DOIUrl":"10.1161/CIRCGEN.125.005523","url":null,"abstract":"<p><strong>Background: </strong>Sudden arrhythmic death syndrome (SADS) refers to sudden cardiac death with structurally normal hearts at autopsy, most frequently attributed to inherited arrhythmia syndromes or concealed cardiomyopathies. Postmortem genetic testing may help identify underlying genetic causes. We aimed to investigate the yield of postmortem genetic testing in SADS cases by determining the prevalence of pathogenic or likely pathogenic variants in channelopathy- and cardiomyopathy-associated genes in autopsy-negative SADS victims.</p><p><strong>Methods: </strong>This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in PROSPERO (REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD420251067244). PubMed and Embase were searched on June 4, 2025, for observational studies including individuals aged 1 to 50 years with SADS and negative or nonspecific findings at autopsy. Eligible studies reported postmortem genetic testing for channelopathy and cardiomyopathy genes. Pathogenic or likely pathogenic variant classification followed American College of Medical Genetics and Genomics criteria and ClinGen gene-disease associations. Pooled prevalence was estimated using random-effects models.</p><p><strong>Results: </strong>A total of 45 studies involving 2498 SADS cases were included. Among 1697 SADS victims tested for both channelopathy and cardiomyopathy genes (33 studies), the pooled prevalence of pathogenic or likely pathogenic variants was 11.1% (95% CI, 4.1%-26.6%, <i>I</i>²=50.7%). Testing for cardiomyopathy genes (33 studies, 1697 cases) and for channelopathy genes (42 studies, 2354 cases) yielded a prevalence of 7.0% (95% CI, 1.9%-22.9%, <i>I</i>²=51.9%) and 6.3% (95% CI, 2.0%-18.4%, <i>I</i>²=49.8%), respectively. The most frequently involved genes encoded sarcomeric proteins and ion channels, with <i>TTN</i>, <i>MYBPC3</i>, <i>MYH7</i>, <i>KCNH2</i>, and <i>SCN5A</i> among the most commonly affected.</p><p><strong>Conclusions: </strong>Postmortem genetic testing identifies pathogenic or likely pathogenic variants in a significant subset of SADS cases, supporting its utility in postmortem evaluation.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e005523"},"PeriodicalIF":6.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}