Circulation: Cardiovascular Genetics最新文献

{"title":"Pathogenicity of Hypertrophic Cardiomyopathy Variants: A Path Forward Together.","authors":"Jodie Ingles, Charlotte Burns, Birgit Funke","doi":"10.1161/CIRCGENETICS.117.001916","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001916","url":null,"abstract":"The challenges of correctly interpreting rare variants identified via genetic testing of patients with hypertrophic cardiomyopathy (HCM) are universal and ever present. HCM genetic testing has been offered for almost 2 decades, yet in spite of the leaps forward in our understanding, the genetic underpinnings of this disease remain elusive in many patients. Mainstream application of comprehensive cardiac gene panels, which are becoming more affordable as the technology develops, detect a clinically significant variant in 40% to 60% of patients with the majority of variants residing in genes encoding the cardiac sarcomere.1,2 The value of identifying a pathogenic variant in a proband extends to family members, who have the option to know conclusively whether they carry the causative variant, allowing more targeted clinical surveillance and clarifying risk to children. For many others, however, the identification of uncertain variants poses greater challenges, and the expertise, resources, and standardized criteria to classify them as causative or benign currently fall short.\u0000\u0000See Article by Furqan et al \u0000\u0000In this issue of Circulation: Cardiovascular Genetics , Furqan et al3 demonstrate the marked discordance seen between specialist HCM centers worldwide. Among sarcomeric human cardiomyopathy registry centers, 20.5% of variants seen in >1 center had classification discrepancies that impacted clinical management, that is, likely pathogenic/pathogenic or variant of uncertain significance or likely benign/benign. The primary reason, in 75% of cases, was access to privately held data by either the sarcomeric human cardiomyopathy registry center (60%) or from the genetic testing laboratory’s internal experience (60%). Segregation information from informative families accounted for 35% of discordant variants, …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35479280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifying Mendel Redux: Unbiased Approaches Can Find Modifiers.","authors":"Kim L McBride, Stephanie M Ware","doi":"10.1161/CIRCGENETICS.117.001891","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001891","url":null,"abstract":"Congenital heart disease (CHD) is one of the most common groups of birth defects,1 contributing to a major portion of mortality in early childhood and consuming large amounts of healthcare and family resources. They have a birth prevalence of 6 to 8/1000 live births, excluding late recognized defects, such as bicuspid aortic valve, which has a population frequency of 1% to 2%.1\u0000\u0000See Article by Guo et al \u0000\u0000Genetic epidemiology studies and reports of multiple recurrences of CHDs within families demonstrate a strong genetic component. Familial clustering of CHDs is particularly apparent when grouped by developmental mechanism.2 A recent large study using hundreds of these multiplex families confirmed the concept of grouping CHD by developmental mechanism, and supporting animal data suggest that these groupings are because of perturbations of genetic networks important in cardiogenesis.3 Indeed, of all risk factors for CHD, a family history of CHD has the highest relative risk even over maternal diabetes mellitus or twinning.4 More formal segregation analyses have confirmed the strong genetic component, also noting that the inheritance pattern is likely complex and oligogenic.2\u0000\u0000This evidence for the genetic basis of CHD spurred investigators to search for responsible loci and genes. A few early successes occurred using the traditional genetic approach of linkage, identifying pathogenic variants in NKX2-5 ,5 NOTCH1 ,6 and GATA4 7 among multiplex families with CHDs. Unfortunately, further successes have been scarce, with the exception of CHDs occurring as part of a syndrome (such as the RASopathies). Genome-wide association studies for specific groups of CHD have added a few more loci but with limited replications in a second study.8,9 Copy number variant studies have identified novel genomic disorders in as many as 20% of syndromic cases, a few percent of nonsyndromic …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001891","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35601881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Height and Incident Risk of Venous Thromboembolism: A Cosibling Design.","authors":"Bengt Zöller,&nbsp;Jianguang Ji,&nbsp;Jan Sundquist,&nbsp;Kristina Sundquist","doi":"10.1161/CIRCGENETICS.116.001651","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.116.001651","url":null,"abstract":"<p><strong>Background: </strong>Body height has been associated with an increased risk of venous thromboembolism (VTE), but the association can be confounded with shared familial factors (genetic/environmental). A cosibling design is useful for deeper understanding about the relationship between VTE and height.</p><p><strong>Methods and results: </strong>From Swedish national registry databases, we used a corelative design with full siblings alongside a general Swedish population sample. A cohort of male conscripts (n=1 610 870), born in 1951 to 1992 without previous VTE, was followed from enlistment (1969-2010) until 2012. Another cohort of first-time pregnant women (n=1 093 342) from the medical birth register, without previous VTE, was followed from first pregnancy (1982-2012) until 2012. Using the Multi-Generation Register, we identified all full-sibling pairs discordant for height. This cosibling design allowed for adjustment for familial factors (genetic/environmental). Compared with the tallest women (>185 cm) and men (>190 cm), there was a graded decreased risk by lower height for both men and women. The risk was lowest in women and men with the shortest stature (<155 and <160 cm, respectively): hazard ratios=0.31 (95% confidence interval, 0.22-0.42) and 0.35 (95% confidence interval, 0.22-0.55), respectively. There was a graded association also in the cosibling design comparing siblings with varying degree of discordance for height (reference was the taller sibling): ≥10 cm difference between brothers hazard ratios=0.69 (95% confidence interval, 0.61-0.78) and sisters hazard ratios=0.65 (95% confidence interval, 0.52-0.80), respectively.</p><p><strong>Conclusions: </strong>Height is an independent predictor of VTE. The use of sibling pairs reduces the likelihood that familial confounding explains the results. The findings are important for the understanding of the pathogenesis of VTE.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.116.001651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35327933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights From the Positive Association of Height With Incident Venous Thromboembolism.","authors":"C Mary Schooling","doi":"10.1161/CIRCGENETICS.117.001911","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001911","url":null,"abstract":"Zoller et al1 clearly show height positively associated with incident venous thromboembolism (VTE) in both men and women using an observational design and a cosibling design in a very large study, including a sizeable segment of the Swedish population, that is, all males born 1951 to 1992 without previous VTE and all first time pregnant women from 1982 to 2012. Despite the large size of the study,1 the observational design is open to bias from confounding by common causes of height and VTE. Inevitably, in a study making cost-effective use of invaluable Swedish registry data, Zoller et al1 were unable to adjust for all potential confounders leaving the study open to bias from residual confounding from unmeasured attributes affecting both height and VTE. For example, they used participant’s educational level as a confounder1 instead of all aspects of parental socioeconomic position which might not fully account for confounding by such an influential, multidimensional attribute as parental socioeconomic position. Residual confounding by parental socioeconomic position could in this instance partially obscure any harmful effects of greater height, meaning that the observational estimate might underestimate any harmful effects of height. Zoller et al1 also adjusted for family history of VTE and body mass index. Family history and body mass index are probably not confounders, because they may cause VTE, they are unlikely to determine height, although height might determine body mass index. As such, the adjusted estimates have also been adjusted for potential mediators, which might attenuate any harmful effects of height, meaning that the observational estimate might be an underestimate. In this situation, the cosibling design is particularly helpful because it makes different assumptions. The cosibling design essentially compares siblings, which automatically controls for measured and unmeasured confounders shared by siblings, such as parental socioeconomic position …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35327934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Smoking-Associated miRNA-mRNA Coexpression Network.","authors":"Mete Civelek","doi":"10.1161/CIRCGENETICS.117.001914","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001914","url":null,"abstract":"Adverse effects of cigarette smoking on our health are well documented. On the other hand, we do not fully understand the mechanisms by which these adverse effects occur. In this issue of Circulation: Cardiovascular Genetics , Willinger et al1 identified a smoking-related microRNA (miRNA)/messenger RNA (mRNA) coexpressed gene network in the whole blood of previous and current smokers. They performed the study as part of the extensive phenotypic characterization performed in the participants of the Framingham Heart Study.2 miRNAs, which are small noncoding RNAs that regulate gene expression by binding to their target mRNAs causing translational repression or target degradation,3 have been recognized for their role in cardiovascular pathology.4–6 The results of the current study add another dimension to previous studies by pointing to dysregulated inflammatory responses in leukocytes by miRNA-specific gene regulatory networks in cigarette smokers.\u0000\u0000See Article by Willinger and Rong et al \u0000\u0000The authors arrived at this conclusion via a series of well-designed experiments. They used total RNA isolated from peripheral whole blood obtained from 5023 nonfasting participants of the Framingham Study. These participants were part of the Offspring and Third Generation cohorts. The mean age of the participants was 55 years old, and 54% of them were female. Ten percent of them were current smokers, 41% were former smokers, and 48% had …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001914","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35449457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QT Interval Determinant: Mutations, Rare Variants, or Single-Nucleotide Polymorphisms?","authors":"Takeshi Aiba,&nbsp;Atsushi Takahashi","doi":"10.1161/CIRCGENETICS.117.001945","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001945","url":null,"abstract":"Long-QT syndrome (LQTS) is typically characterized by QT interval prolongation on ECG associated with syncope or sudden cardiac death in young individuals when prolongation of the QT interval induces torsade de pointes, a polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation.1 LQTS is characterized by mutations in several ion channel genes. Although >10 susceptible genes have been identified, KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3) are the most common LQTS genes, accounting for ≈90% of all genotype-positive cases. Only <5% of cases are diagnosed as LQT4~15, and 20% to 30% of cases remain genetically elusive. In the past 2 decade, lots of LQTS clinical databases have revealed genotype–phenotype correlations in the 3 major LQTS (LQT1~3) subtypes and have indicated that the genotype, together with QTc interval, age, and sex, is a determinant of arrhythmic risk and response to medication therapy.2 Furthermore, not only genotype but also mutation site–specific differences in arrhythmic risk could be reported in LQT1 and LQT2.3,4\u0000\u0000See Article by Rosenberg et al \u0000\u0000However, as in most Mendelian disorders, patient management is complicated by the variability in disease severity among LQTS mutation carriers.5 Even in the same mutation, for example, KCNQ1 -A341V, mutation carriers had a wide range of QTc values (406–676 ms), and 12% of individuals had a normal QTc (≤440 ms).6 Furthermore, in addition to the LQTS-causing gene mutations, other genetic polymorphisms, such as NOS1AP , KCNE1 -D85N may affect the QT …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001945","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35479282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter by Brewster Regarding Article, \"<i>CKM</i> Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia\".","authors":"Lizzy M Brewster","doi":"10.1161/CIRCGENETICS.117.001938","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001938","url":null,"abstract":"In a recent article, Siddiqui et al1 aimed to gain insight in the known negative association between constitutive plasma creatine kinase (CK) and a rare single-nucleotide polymorphism in the CK gene coding for the cytoplasmic M isoenzyme monomer, CKM Glu83Gly (rs11559024). The authors report that the polymorphism is associated with lower plasma CK variability and inducibility, but not with myalgia. It is concluded that the findings represent a novel mechanistic rationale for a subpopulation of individuals presenting with statin intolerance or myalgia without raised CK levels.1 Although the data are promising, the authors should have included cytoplasmic CK in the discussion.\u0000\u0000There is no …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35569343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Pressure Genome-Wide Association Studies, Missing Heritability, and Omnigenics.","authors":"Brian J Morris","doi":"10.1161/CIRCGENETICS.117.001943","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001943","url":null,"abstract":"The past 4 decades have seen enormous progress toward understanding the genetic basis of complex polygenic traits. In the hypertension field, the search began with a simple association study of a restriction fragment length polymorphism in the human renin gene in 1988.1 Although the result was negative, it was followed by a plethora of studies comparing allele frequencies of polymorphisms in potential candidate genes in subjects with essential hypertension with allele frequencies in subjects with normal blood pressure. There were also linkage studies involving pedigrees affected by rare monogenic forms of hypertension. Soon, positive results began to emerge for essential hypertension2,3 and in identification of single gene mutations responsible for various forms of familial hypertension.4 In addition, linkage analyses were used to identify hypertension loci in rat models of hypertension5 and in essential hypertension. Positive findings from the human studies emerged from sib-pair analysis of restriction fragment length polymorphisms at the angiotensinogen gene locus on chromosome 1,3 in a sib-pair study of microsatellite markers spanning all of chromosome 1,6 and by genome-wide linkage analysis.7–9 Next came large-scale genome-wide association studies (GWAS) involving single nucleotide polymorphisms (SNPs) aimed at identification of all genetic loci for blood pressure and essential hypertension.10 These became, and remain, the tour de force for studies of complex polygenic diseases. More recently, transcriptome-wide studies have been undertaken.11 These identify, but do not discriminate between, genes that are either directly or indirectly involved in hypertension. The first human study, my my Lab, resulted in the comprehensive identification of numerous messenger RNAs and microRNAs differentially expressed in the kidney in essential hypertension.11 The study further identified a potential causative mechanism whereby microRNA-mediated repression of the renin gene is lost in hypertensives, so increasing renal renin …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001943","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35449458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of Polygenic Scores for QT Interval in Clinical Populations.","authors":"Michael A Rosenberg,&nbsp;Steven A Lubitz,&nbsp;Honghuang Lin,&nbsp;Gulum Kosova,&nbsp;Victor M Castro,&nbsp;Paul Huang,&nbsp;Patrick T Ellinor,&nbsp;Roy H Perlis,&nbsp;Christopher Newton-Cheh","doi":"10.1161/CIRCGENETICS.117.001724","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001724","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PGS) enable rapid estimation of genome-wide susceptibility for traits, which may be useful in clinical settings, such as prediction of QT interval. In this study, we sought to validate PGS for QT interval in 2 real-world cohorts of European ancestry (EA) and African ancestry (AA).</p><p><strong>Methods and results: </strong>Two thousand nine hundred and fifteen participants of EA and 366 of AA in the MGH CAMP study (Cardiology and Metabolic Patient) were genotyped on a genome-wide array and imputed to the 1000 Genomes reference panel. An additional 820 EA and 57 AA participants in the Partners Biobank were genotyped and used for validation. PGS were created for each individual using effect estimates from association tests with QT interval obtained from prior genome-wide association studies, with variants selected based from multiple significance thresholds in the original study. In regression models, clinical variables explained ≈9% to 10% of total variation in resting QTc in EA individuals and ≈12% to 18% in AA individuals. The PGS significantly increased variation explained at most significance thresholds (<i>P</i><0.001), with a trend toward increased variation explained at more stringent <i>P</i> value cut points in the CAMP EA cohort (<i>P</i><0.05). In AA individuals, PGS provided no improvement in variation explained at any significance threshold.</p><p><strong>Conclusions: </strong>For individuals of European descent, PGS provided a significant increase in variation in QT interval explained compared with a model with only nongenetic factors at nearly every significance level. There was no apparent benefit gained by relaxing the significance threshold from conventional genome-wide significance (<i>P</i><5×10^-⁸).</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35479276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Triangulation and Coverage Analysis in Whole-Exome Sequencing-Based Molecular Autopsies.","authors":"Garrett W Shanks,&nbsp;David J Tester,&nbsp;Sneha Nishtala,&nbsp;Jared M Evans,&nbsp;Michael J Ackerman","doi":"10.1161/CIRCGENETICS.117.001828","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001828","url":null,"abstract":"<p><strong>Background: </strong>WEMA (Whole-Exome Molecular Autopsy) and surveillance of cardiac channelopathy and cardiomyopathy genes represents the latest molecular autopsy for sudden death in the young (SDY). To date, the majority of WEMA has been performed on the SDY case only.</p><p><strong>Methods and results: </strong>We performed whole-exome sequencing and nucleotide-level coverage analysis on 28 SDY cases (18.4±7.8 years) and their parents to determine the inheritance patterns of ultrarare, nonsynonymous variants in 99 sudden death-susceptibility genes. Nonsynonymous variants were adjudicated using the American College of Medical Genetics guidelines. Overall, 17 sudden death-susceptibility gene variants were identified in 12 of 28 (43%) SDY cases. On the basis of the American College of Medical Genetics guidelines, 6 of 28 (21%) cases had a pathogenic or likely pathogenic nonsynonymous variant with 3 (50%) being de novo. Two nonsynonymous variants would not have been elevated to likely pathogenic status without knowing their de novo status. Whole-exome sequencing reached a read depth of 10× across 90% of nucleotides within sudden death-susceptibility genes in 100% of parental exomes from fresh blood draw, compared with only 82% of autopsy-sourced SDY exomes.</p><p><strong>Conclusions: </strong>An SDY-parent, trio-based WEMA may be an effective way of elucidating a monogenic cause of death and bringing clarity to otherwise ambiguous variants. If other studies confirm this relatively high rate of SDY cases stemming from de novo mutations, then the WEMA should become even more cost-effective given that the decedent's first-degree relatives should only need minimal cardiological evaluation. In addition, autopsy-sourced DNA demonstrated strikingly lower whole-exome sequencing coverage than DNA from fresh blood draw.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35479277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}