Circulation: Cardiovascular Genetics最新文献

{"title":"Effect of Disclosing Genetic Risk for Coronary Heart Disease on Information Seeking and Sharing: The MI-GENES Study (Myocardial Infarction Genes).","authors":"Sherry-Ann N Brown,&nbsp;Hayan Jouni,&nbsp;Tariq S Marroush,&nbsp;Iftikhar J Kullo","doi":"10.1161/CIRCGENETICS.116.001613","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.116.001613","url":null,"abstract":"<p><strong>Background: </strong>Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. We hypothesized that disclosing genetic risk for CHD to individuals influences information seeking and sharing.</p><p><strong>Methods and results: </strong>The MI-GENES study (Myocardial Infarction Genes) randomized participants (n=203) aged 45 to 65 years who were at intermediate CHD risk based on conventional risk factors and not on statins to receive their conventional risk score alone or also a genetic risk score based on 28 variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys assessing information seeking were completed before and after risk disclosure. Information sharing was assessed post-disclosure. Six-month post-disclosure, genetic risk score participants were more likely than conventional risk score participants to visit a website to learn about CHD (odds ratio [OR], 4.88 [confidence interval (CI), 1.55-19.13]; <i>P</i>=0.01), use the internet for information about how genetic factors affect CHD risk (OR, 2.11 [CI, 1.03-4.47]; <i>P</i>=0.04), access their CHD risk via a patient portal (OR, 2.99 [CI, 1.35-7.04]; <i>P</i>=0.01), and discuss their CHD risk with others (OR, 3.13 [CI, 1.41-7.47]; <i>P</i>=0.01), particularly their siblings (OR, 1.92 [CI, 1.06-3.51]; <i>P</i>=0.03), extended family (OR, 3.8 [CI, 1.37-12.38]; <i>P=</i>0.01), coworkers (OR, 2.42 [CI, 1.09-5.76]; <i>P</i>=0.03), and primary care provider (PCP; OR, 2.00 [CI, 1.08-3.75]; <i>P</i>=0.03).</p><p><strong>Conclusions: </strong>Disclosure of a genetic risk score for CHD increased information seeking and sharing.</p><p><strong>Clinical trial registration: </strong>URL: https://clinicaltrials.gov/. Unique identifier: NCT01936675.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.116.001613","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35384203","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":"<i>PCSK9</i> Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From 9 Studies of Blacks and Whites.","authors":"Shia T Kent, Robert S Rosenson, Christy L Avery, Yii-Der I Chen, Adolfo Correa, Steven R Cummings, L Adrienne Cupples, Mary Cushman, Daniel S Evans, Vilmundur Gudnason, Tamara B Harris, George Howard, Marguerite R Irvin, Suzanne E Judd, J Wouter Jukema, Leslie Lange, Emily B Levitan, Xiaohui Li, Yongmei Liu, Wendy S Post, Iris Postmus, Bruce M Psaty, Jerome I Rotter, Monika M Safford, Colleen M Sitlani, Albert V Smith, James D Stewart, Stella Trompet, Fangui Sun, Ramachandran S Vasan, J Michael Woolley, Eric A Whitsel, Kerri L Wiggins, James G Wilson, Paul Muntner","doi":"10.1161/CIRCGENETICS.116.001632","DOIUrl":"10.1161/CIRCGENETICS.116.001632","url":null,"abstract":"<p><strong>Background: </strong><i>PCSK9</i> loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of <i>PCSK9</i> LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy.</p><p><strong>Methods and results: </strong>These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between <i>PCSK9</i> LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, <i>PCSK9</i> LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. <i>PCSK9</i> LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. <i>PCSK9</i> LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites).</p><p><strong>Conclusions: </strong><i>PCSK9</i> LOF variants were associated with lower LDL-C and coronary heart disease incidence. <i>PCSK9</i> LOF variants were not associated with stroke risk.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001632"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729040/pdf/nihms889818.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284645","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":"The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association.","authors":"Kiran Musunuru,&nbsp;Erik Ingelsson,&nbsp;Myriam Fornage,&nbsp;Peter Liu,&nbsp;Anne M Murphy,&nbsp;L Kristin Newby,&nbsp;Christopher Newton-Cheh,&nbsp;Marco V Perez,&nbsp;Deepak Voora,&nbsp;Daniel Woo","doi":"10.1161/HCG.0000000000000037","DOIUrl":"https://doi.org/10.1161/HCG.0000000000000037","url":null,"abstract":"<p><p>There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the \"expressed genome.\" The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/HCG.0000000000000037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35277962","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":"Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events.","authors":"Jan P Dumanski,&nbsp;Johan Sundström,&nbsp;Lars A Forsberg","doi":"10.1161/CIRCGENETICS.117.001820","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001820","url":null,"abstract":"It has been observed for centuries that men have a shorter lifespan than women. The current difference globally is on average 4 years, and the difference is even larger in populations with longer life expectancy, for example, ≈6 years in the European Union and 7 years in Japan.1 A larger difference in populations with higher longevity suggests that the underlying factors are stronger in populations with a large part of the mortality related to age-associated diseases. Cardiovascular diseases are the leading causes of death globally and are increasing.2 The share of total mortality that is because of cardiovascular diseases is similar in both sexes, but men fall ill and die from it at a younger age. Cardiovascular disease risk factors are equally important for men and women.3 Hence, the age differences in incidence and mortality between men and women are because of other reasons than differential environmental risk factor exposures. Recent discoveries on pathological effects from a male-specific genetic risk factor—loss of chromosome Y (LOY) in blood cells—can partly explain the observed sex difference in longevity. Analyses by Haitjema et al4 in this issue of Circulation: Cardiovascular Genetics describe a previously unknown association between LOY in blood cells and major cardiovascular events.\u0000\u0000See Article by Haitjema et al \u0000\u0000A high prevalence …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001820"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284646","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":"Informational Quest.","authors":"Susanne B Haga","doi":"10.1161/CIRCGENETICS.117.001860","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001860","url":null,"abstract":"","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35384206","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":"CKing Precision in the Interpretation of Diagnostic Biomarkers.","authors":"Simon de Denus,&nbsp;Jean-Claude Tardif,&nbsp;Marie-Pierre Dubé","doi":"10.1161/CIRCGENETICS.117.001874","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001874","url":null,"abstract":"Creatine kinase (CK) is a dimeric globular protein that includes 2 subunits.1 The different combinations of the 2 subunits of the CK dimer, CK-M and CK-B, lead to 3 isoforms of the cytoplasmic enzyme.2 CK-MM is primarily expressed in skeletal muscles and represents the greater part of serum CK. Two isoenzymes also exist in mitochondria.1 From a physiological perspective, CK is vital to catalyze the reversible exchange of high-energy phosphate bonds, which is crucial for energy buffering in tissues with variable energy demand, such as skeletal muscles.1 From a clinical perspective, the measurement of CK, a biomarker of muscle damage,3 is a routine part of the assessment of patients with several conditions.\u0000\u0000See Article by Siddiqui et al \u0000\u0000A frequent use of CK as a biomarker is in the assessment of patients with muscle pain or weakness while being treated with a statin, which is now broadly referred to as statin-associated muscle symptoms (SAMS).4,5 Because muscle aches and pains are unspecific, subjective, and frequently observed with multiple common conditions, CK measurement is a key component in the evaluation of patients reporting SAMS to identify those at risk of more severe muscle problems, such as myopathy or rhabdomyolysis (severe myopathy in the presence of myoglobinemia or myoglobinuria and renal impairment/failure).5 Fortunately, severe SAMS accompanied with CK elevation >10× the upper reference limit (URL) are extremely rare, occurring in 1 per 1000 to 1 per 10 000 patients per year.5\u0000\u0000For the clinician, muscle symptoms in the presence of no or only minor to modest CK elevations represent a particular challenge to discriminate SAMS from other secondary causes (hypothyroidism, other drugs). In the case the former is suspected, this often leads to a laborious exercise, for both the patient and the clinician, that …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35393655","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":"Carotid Plaque Rupture Is Accompanied by an Increase in the Ratio of Serum circR-284 to miR-221 Levels.","authors":"Hernan A Bazan,&nbsp;Samuel A Hatfield,&nbsp;Aaron Brug,&nbsp;Ashton J Brooks,&nbsp;Daniel J Lightell,&nbsp;T Cooper Woods","doi":"10.1161/CIRCGENETICS.117.001720","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001720","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerotic plaque rupture is accompanied by an acute decrease in the carotid plaque expression of micro-RNAs (miRs)-221 and miR-222. Circular RNA (circR)-284 is a potential inhibitor of miR-221/miR-222 activity. We aimed to determine whether changes in the serum levels of these noncoding RNAs are observed in patients with asymptomatic high-grade carotid disease versus patients with acutely symptomatic carotid disease and recent ischemic stroke. Additionally, we tested the use of functionally related noncoding RNA pairs to enhance the discriminatory power of noncoding RNAs as circulating biomarkers.</p><p><strong>Methods and results: </strong>Serum levels of miR-221, miR-222, miR-145, and circR-284 were measured in 24 asymptomatic (asymptomatic) and 17 acutely symptomatic patients ([urgent] ischemic cerebrovascular event within the previous 5 days) undergoing carotid endarterectomy. miR-221 was significantly lower, whereas circR-284 was elevated in the serum of the urgent compared with the asymptomatic group. The ratio of serum circR-284:miR-221 was significantly elevated in the urgent group (<i>P</i>=0.0002) and exhibited favorable characteristics as a biomarker indicative of carotid plaque rupture and stroke. A validation study in 112 patients (47 asymptomatic, 41 urgent, and 24 patients with a cerebrovascular event between 5 and 180 days of the carotid endarterectomy [symptomatic]) confirmed elevation of serum circR-284:miR-221 uniquely in the urgent group (<i>P</i><0.001) and favorable sensitivity and specificity for detecting plaque rupture and stroke.</p><p><strong>Conclusions: </strong>Serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid plaque rupture and stroke. Moreover, we demonstrate the use of functionally related pairs of circulating noncoding RNAs as biomarkers in cardiovascular disease.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35384204","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":"Previously Unreported in Women <i>Galactosidase Alpha</i> Pro409Ser Variant Is Associated With Fabry Disease.","authors":"Sushil Allen Luis,&nbsp;Joseph J Maleszewski,&nbsp;Phillip M Young,&nbsp;Hartzell V Schaff,&nbsp;Naveen L Pereira","doi":"10.1161/CIRCGENETICS.116.001661","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.116.001661","url":null,"abstract":"Fabry disease is a rare X-linked lysosomal storage disorder involving a deficiency in α- galactosidase A. This condition results in an impaired ability to metabolize globotriaosylceramide in the glycosphingolipid metabolic pathway, which accumulates within tissues throughout the body. Fabry disease affects 1 in 40 000 to 117 000 men with an unknown prevalence in women.1 Clinical presentations can be variable, ultimately resulting in potentially severe end-organ damage. In light of the variability in clinical presentation and rarity of the disease, initial misdiagnosis is common with a mean delay to diagnosis of between 13.7 and 16.3 years from symptom onset.1 Typical manifestations can include cutaneous lesions (angiokeratoma corporis), peripheral neuropathy, cerebrovascular accidents, proteinuria, renal insufficiency, and cardiac dysfunction.2,3 Cardiac manifestations include increased ventricular wall thickness, heart failure, valvular thickening and dysfunction, and coronary artery disease.2,3 Accurate and early diagnosis is imperative because early treatment with agalsidase β had been demonstrated to reduce the incidence of major adverse outcomes, including renal failure, stroke, cardiac events, and death.2\u0000\u0000A 50-year-old woman presented to our institution with a recent onset of worsening exertional shortness of breath, fatigue, and chest tightness on a background of a presumptive diagnosis of hypertrophic cardiomyopathy made 10 years before. Her family history was significant for ischemic heart disease in her father and brother and valvular disease in her sister, but there was no known family history of hypertrophic cardiomyopathy. There were no other systemic symptoms, and clinical examination revealed a holosystolic murmur without other features of systemic disease, including cornea verticillata. Baseline renal function was normal with a creatinine of 0.8 mg/dL. Echocardiography (Figure 1A and 1B) demonstrated severe concentric increase in left ventricular wall thickness with systolic anterior motion of the mitral valve leaflets resulting in severe left ventricular outflow tract …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":"e001661"},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.116.001661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284644","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":"Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction.","authors":"Karol Miszalski-Jamka,&nbsp;John L Jefferies,&nbsp;Wojciech Mazur,&nbsp;Jan Głowacki,&nbsp;Jianhong Hu,&nbsp;Monika Lazar,&nbsp;Richard A Gibbs,&nbsp;Jacek Liczko,&nbsp;Jan Kłyś,&nbsp;Eric Venner,&nbsp;Donna M Muzny,&nbsp;Jarosław Rycaj,&nbsp;Jacek Białkowski,&nbsp;Ewa Kluczewska,&nbsp;Zbigniew Kalarus,&nbsp;Shalini Jhangiani,&nbsp;Hussein Al-Khalidi,&nbsp;Tomasz Kukulski,&nbsp;James R Lupski,&nbsp;William J Craigen,&nbsp;Matthew N Bainbridge","doi":"10.1161/CIRCGENETICS.117.001763","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001763","url":null,"abstract":"<p><strong>Background: </strong>Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous disease and, although increasingly recognized in clinical practice, there is a lack of widely accepted diagnostic criteria. We sought to identify novel genetic causes of LVNC and describe genotype-phenotype correlations.</p><p><strong>Methods and results: </strong>A total of 190 patients from 174 families with left ventricular hypertrabeculation (LVHT) or LVNC were referred for cardiac magnetic resonance and whole-exome sequencing. A total of 425 control individuals were included to identify variants of interest (VOIs). We found an excess of 138 VOIs in 102 (59%) unrelated patients in 54 previously identified LVNC or other known cardiomyopathy genes. VOIs were found in 68 of 90 probands with LVNC and 34 of 84 probands with LVHT (76% and 40%, respectively; <i>P</i><0.001). We identified 0, 1, and ≥2 VOIs in 72, 74, and 28 probands, respectively. We found increasing number of VOIs in a patient strongly correlated with several markers of disease severity, including ratio of noncompacted to compacted myocardium (<i>P</i><0.001) and left ventricular ejection fraction (<i>P</i>=0.01). The presence of sarcomeric gene mutations was associated with increased occurrence of late gadolinium enhancement (<i>P</i>=0.004).</p><p><strong>Conclusions: </strong>LVHT and LVNC likely represent a continuum of genotypic disease with differences in severity and variable phenotype explained, in part, by the number of VOIs and whether mutations are present in sarcomeric or nonsarcomeric genes. Presence of VOIs is common in patients with LVHT. Our findings expand the current clinical and genetic diagnostic approaches for patients with LVHT and LVNC.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001763","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35401815","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":"Genetics of Congenital Heart Disease: Is the Glass Now Half-Full?","authors":"Linda Leatherbury,&nbsp;Charles I Berul","doi":"10.1161/CIRCGENETICS.117.001746","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001746","url":null,"abstract":"Congenital heart defects are present in 1% of all live births and are a significant burden on the parents and family, healthcare system, and overall community. Congenital heart defects (CHD) are also identified in 10% of still births and are presumed to be a substantial cause of early fetal demise. With advances in prenatal diagnosis, corrective strategies, and longitudinal care, infant mortality has substantially declined. Today >75% of CHD children who survive the first year of live will enter into adulthood. Elucidating the cause of an offspring’s CHD is greatly valued by parents, providing comfort that the defect was because of genetic randomness beyond their control and that certain problems arise from the same underlying genetic issue and not from preventable errors.1 As Helen Taussig stated 50 years ago “Our next great step forward will come in the field of cause and prevention of malformations.”2 Causes of CHD are often divided into genetic and nongenetic influences. The advantage of contemporary genomic technologies including single-nucleotide polymorphism (SNP) arrays, next-generation sequencing, and copy-number variant platforms are accelerating the discovery of genetic causes of CHD. Importantly, these tools enable the study of sporadic cases, the most common presentation of CHD. A review article summarizing this field entitled the “Genetics of Congenital Heart Disease: The Glass Half-Empty” previously highlighted the limitations of genetic technologies for assigning causality.3 Articles such as the present one in this journal entitled “Genome-Wide Association Studies and Meta-analysis for Congenital Heart Defects”4 are important studies performed using distinct patient cohorts from multiple sites. We are now looking for the complex multigenetic explanations for CHD in a multifactorial scheme, including epigenetic and environmental factors. There is renewed optimism in the field such that today we would see the genetics of CHD but hopefully now with the …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":"10 3","pages":"e001746"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34963958","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}