Circulation: Cardiovascular Genetics最新文献

{"title":"Correction.","authors":"","doi":"10.1161/HCG.0000000000000041","DOIUrl":"https://doi.org/10.1161/HCG.0000000000000041","url":null,"abstract":"","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/HCG.0000000000000041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36849922","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":"Genome-Wide Association Studies Revealing the Heritability of Common Atrial Fibrillation: Is Bigger Always Better?","authors":"Sebastian Clauss, Moritz F Sinner, Stefan Kääb","doi":"10.1161/CIRCGENETICS.117.002005","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.002005","url":null,"abstract":"In this issue of Circulation Cardiovascular Genetics, Weng et al1 present an interesting study evaluating the heritability of atrial fibrillation (AF).\u0000\u0000See Article by Weng et al \u0000\u0000AF is the most common arrhythmia worldwide, and substantial efforts have been made to elucidate mechanisms underlying its onset and progression.2 Over the past years, a growing body of evidence demonstrated that AF is heritable. Besides rare genetic mutations with strong effects and a clear phenotype, such as gain- or loss-of-function mutations in ion channel genes,3–5 there are common genetic variants or single nucleotide polymorphisms that have been shown to be associated with AF although a causal mechanistic role has not been identified for most of the risk variants.6–11 Several studies tried to evaluate the degree of heritability by family-based or population-based studies, such as the Danish twin study that reported an AF heritability of 62% or the Framingham Heart Study that showed a 40% risk to develop AF if a first-degree relative is affected.12,13\u0000\u0000Those numbers raised some concerns because studies performed in families might not adequately mirror the situation in the general population and might hence overestimate the true heritability. Also, it is in contrast to the experience from daily clinical practice where AF is predominantly seen in older patients with comorbidities, that is, in patients with several likely causes for AF, making a genetic cause of the disease less likely. It, therefore, remained unclear to which degree AF can be …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.002005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653278","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":"Genes in the Basement, Postmortem Genetic Testing…and 3 (New) Realities.","authors":"Michael A Seidman, Richard N Mitchell","doi":"10.1161/CIRCGENETICS.117.002008","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.002008","url":null,"abstract":"We all have a treasure trove of things—squirreled away in knick-knack drawers or long-forgotten boxes in the basement, storage lockers, and parents’ homes. Things we tell ourselves will someday have value if we just wait long enough. Every pathology department has things too—the glass slides and paraffin blocks of specimens long since diagnosed and discarded, all tucked away in the far recesses of hospitals and storage warehouses, waiting for a time to reach their full potential. A select few of these even manage to be resurrected each year, some for a retrospective analysis of one marker or another, others to settle a diagnostic or medicolegal matter. Most, however, sit idly in file cabinets and storage facilities, out of sight and largely forgotten, reminiscent of the final scene in Raiders of the Lost Ark.\u0000\u0000See Article by Baudhuin et al \u0000\u0000Those materials, however, still have great value. Among pathologists, this is not exactly a secret—archived slides and blocks have long been appropriated for developing new stains, defining diagnoses, and understanding disease pathogenesis. And when modern genetic testing methods arrived, many had visions of Jurassic Park-style moments, unlocking the secrets embedded not in amber but in paraffin.\u0000\u0000Unfortunately, most of the promise of such materials has languished.\u0000\u0000Genetic testing methods to date have largely focused on peripheral blood and carefully preserved tissues gathered from living patients. Applying the same techniques to the stuff …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.002008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653279","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":"Personalized Anticoagulation: Optimizing Warfarin Management Using Genetics and Simulated Clinical Trials.","authors":"Kourosh Ravvaz,&nbsp;John A Weissert,&nbsp;Christian T Ruff,&nbsp;Chih-Lin Chi,&nbsp;Peter J Tonellato","doi":"10.1161/CIRCGENETICS.117.001804","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001804","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials testing pharmacogenomic-guided warfarin dosing for patients with atrial fibrillation have demonstrated conflicting results. Non-vitamin K antagonist oral anticoagulants are expensive and contraindicated for several conditions. A strategy optimizing anticoagulant selection remains an unmet clinical need.</p><p><strong>Methods and results: </strong>Characteristics from 14 206 patients with atrial fibrillation were integrated into a validated warfarin clinical trial simulation framework using iterative Bayesian network modeling and a pharmacokinetic-pharmacodynamic model. Individual dose-response for patients was simulated for 5 warfarin protocols-a fixed-dose protocol, a clinically guided protocol, and 3 increasingly complex pharmacogenomic-guided protocols. For each protocol, a complexity score was calculated using the variables predicting warfarin dose and the number of predefined international normalized ratio (INR) thresholds for each adjusted dose. Study outcomes included optimal time in therapeutic range ≥65% and clinical events. A combination of age and genotype identified different optimal protocols for various subpopulations. A fixed-dose protocol provided well-controlled INR only in normal responders ≥65, whereas for normal responders <65 years old, a clinically guided protocol was necessary to achieve well-controlled INR. Sensitive responders ≥65 and <65 and highly sensitive responders ≥65 years old required pharmacogenomic-guided protocols to achieve well-controlled INR. However, highly sensitive responders <65 years old did not achieve well-controlled INR and had higher associated clinical events rates than other subpopulations.</p><p><strong>Conclusions: </strong>Under the assumptions of this simulation, patients with atrial fibrillation can be triaged to an optimal warfarin therapy protocol by age and genotype. Clinicians should consider alternative anticoagulation therapy for patients with suboptimal outcomes under any warfarin protocol.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653860","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":"Familial Aggregation of Aortic Valvular Stenosis: A Nationwide Study of Sibling Risk.","authors":"Andreas Martinsson,&nbsp;Xinjun Li,&nbsp;Bengt Zöller,&nbsp;Pontus Andell,&nbsp;Charlotte Andersson,&nbsp;Kristina Sundquist,&nbsp;J Gustav Smith","doi":"10.1161/CIRCGENETICS.117.001742","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001742","url":null,"abstract":"<p><strong>Background: </strong>Aortic valvular stenosis (AS) is the most common cause of cardiac valvular replacement surgery. During the last century, the pathogenesis of AS has undergone transitions in developed countries, from rheumatic heart disease to a degenerative calcific pathogenesis. Although a familial component has been described for a subset of cases with a bicuspid valve, data are limited on the overall familial aggregation of this disease.</p><p><strong>Methods and results: </strong>Contemporary information on 6 117 263 Swedish siblings, of which 13 442 had a clinical diagnosis of AS, was collected from the nationwide Swedish Multi-Generation Register and the National Patient Register. A total of 4.8% of AS cases had a sibling history of AS. Having at least 1 sibling with AS was associated with a hazard ratio of 3.41 (95% confidence interval, 2.23-5.21) to be diagnosed with AS in an adjusted model. Individuals with >1 sibling with AS had an exceptionally high risk (hazard ratio, 32.84) but were uncommon (34 siblings from 11 sibships). In contrast, spouses of subjects with AS were only slightly more likely to be diagnosed with AS compared with subjects without spousal AS (hazard ratio 1.16 for husbands and 1.18 for wives).</p><p><strong>Conclusions: </strong>A sibling history of clinically diagnosed AS was associated with increased risk of AS. Spouses of patients with AS only had a modest risk increase, suggesting that shared adult environmental factors contribute less to the development of AS than genetic factors.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35657834","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":"Applying High-Resolution Variant Classification to Cardiac Arrhythmogenic Gene Testing in a Demographically Diverse Cohort of Sudden Unexplained Deaths.","authors":"Ying Lin,&nbsp;Nori Williams,&nbsp;Dawei Wang,&nbsp;William Coetzee,&nbsp;Bo Zhou,&nbsp;Lucy S Eng,&nbsp;Sung Yon Um,&nbsp;Ruijun Bao,&nbsp;Orrin Devinsky,&nbsp;Thomas V McDonald,&nbsp;Barbara A Sampson,&nbsp;Yingying Tang","doi":"10.1161/CIRCGENETICS.117.001839","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001839","url":null,"abstract":"<p><strong>Background: </strong>Genetic variant interpretation contributes to testing yield differences reported for sudden unexplained death. Adapting a high-resolution variant interpretation framework, which considers disease prevalence, reduced penetrance, genetic heterogeneity, and allelic contribution to determine the maximum tolerated allele count in gnomAD, we report an evaluation of cardiac channelopathy and cardiomyopathy genes in a large, demographically diverse sudden unexplained death cohort that underwent thorough investigation in the United States' largest medical examiner's office.</p><p><strong>Methods and results: </strong>The cohort has 296 decedents: 147 Blacks, 64 Hispanics, 49 Whites, 22 Asians, and 14 mixed ethnicities; 142 infants (1 to 11 months), 39 children (1 to 17 years), 74 young adults (18 to 34 years), and 41 adults (35 to 55 years). Eighty-nine cardiac disease genes were evaluated. Using a high-resolution variant interpretation workflow, we classified 17 variants as pathogenic or likely pathogenic (2 of which were incidental findings and excluded in testing yield analysis), 46 novel variants of uncertain significance, and 130 variants of uncertain significance. Nine pathogenic or likely pathogenic variants in ClinVar were reclassified to likely benign and excluded in testing yield analysis. The yields of positive cases by ethnicity and age were 21.4% in mixed ethnicities, 10.2% Whites, 4.5% Asians, 3.1% Hispanics, and 2% Blacks; 7.7% children, 7.3% in adults, 5.4% young adults, and 2.8% infants. The percentages of uncertain cases with variants of uncertain significance by ethnicity were 45.5% in Asians, 45.3% Hispanics, 44.20% Blacks, 36.7% Whites, and 14.3% in mixed ethnicities.</p><p><strong>Conclusions: </strong>High-resolution variant interpretation provides diagnostic accuracy and healthcare efficiency. Under-represented populations warrant greater inclusion in future studies.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35661571","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":"Genetic Testing in Pediatric Left Ventricular Noncompaction.","authors":"Erin M Miller,&nbsp;Robert B Hinton,&nbsp;Richard Czosek,&nbsp;Angela Lorts,&nbsp;Ashley Parrott,&nbsp;Amy R Shikany,&nbsp;Richard F Ittenbach,&nbsp;Stephanie M Ware","doi":"10.1161/CIRCGENETICS.117.001735","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001735","url":null,"abstract":"<p><strong>Background: </strong>Left ventricular noncompaction (LVNC) can occur in isolation or can co-occur with a cardiomyopathy phenotype or cardiovascular malformation. The yield of cardiomyopathy gene panel testing in infants, children, and adolescents with a diagnosis of LVNC is unknown. By characterizing a pediatric population with LVNC, we sought to determine the yield of cardiomyopathy gene panel testing, distinguish the yield of testing for LVNC with or without co-occurring cardiac findings, and define additional factors influencing genetic testing yield.</p><p><strong>Methods and results: </strong>One hundred twenty-eight individuals diagnosed with LVNC at ≤21 years of age were identified, including 59% with idiopathic pathogenesis, 32% with familial disease, and 9% with a syndromic or metabolic diagnosis. Overall, 75 individuals had either cardiomyopathy gene panel (n=65) or known variant testing (n=10). The yield of cardiomyopathy gene panel testing was 9%. The severity of LVNC by imaging criteria was not associated with positive genetic testing, co-occurring cardiac features, pathogenesis, family history, or myocardial dysfunction. Individuals with isolated LVNC were significantly less likely to have a positive genetic testing result compared with those with LVNC and co-occurring cardiomyopathy (0% versus 12%, respectively; <i>P</i><0.01).</p><p><strong>Conclusions: </strong>Genetic testing should be considered in individuals with cardiomyopathy co-occurring with LVNC. These data do not suggest an indication for cardiomyopathy gene panel testing in individuals with isolated LVNC in the absence of a family history of cardiomyopathy.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35318159","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":"Calcific Aortic Valve Disease: Insights Into the Genetics of Vascular Ageing.","authors":"Richmond W Jeremy","doi":"10.1161/CIRCGENETICS.117.002012","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.002012","url":null,"abstract":"The shifting global demographic profile toward an older population is well recognized and carries with it the increased burden of degenerative cardiovascular disease, with associated morbidity, mortality, and healthcare costs. Vascular ageing is characterized by increased arterial stiffness, systolic arterial hypertension, myocardial thickening and fibrosis, and associated atherosclerosis.1\u0000\u0000See Article by Martinsson et al \u0000\u0000Calcific aortic valve stenosis (CAVS) is another manifestation and affects ≈1 in 30 people aged 75 years. Furthermore, CAVS is associated with several adverse vascular risk factors, including hypertension, hypercholesterolemia, and diabetes mellitus, as well as with underlying structural abnormalities, for example, bicuspid aortic valve.\u0000\u0000Considerable resources are already devoted to health care consequent on vascular ageing and the load is increasing—as evidenced by the burgeoning need for operative and percutaneous aortic valve replacements.2 If society is to better manage health costs for the older population, we need to better understand the mechanisms of vascular ageing and thereby develop and implement novel preventive strategies.\u0000\u0000There is significant familial risk for atherosclerotic vascular disease, beyond familial hypercholesterolemia and hypertension, although the actual genetic factors responsible remain elusive. In this issue of Circulation: Cardiovascular Genetics , Martinsson et al3 present evidence for a significant familial risk for CAVS in the general population. At the same time, there is also a lesser, but nonetheless significant, environmental risk.\u0000\u0000The fascinating question is how we might explain these observations and whether we can now begin to formulate a hypothesis about why some individuals develop CAVS.\u0000\u0000A systolic ejection murmur is a common finding in older patients and echocardiography has shown us that most individuals develop some thickening and restriction of leaflet motion of the aortic valve with increasing age. Despite this, most …","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.002012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35657833","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":"Technical Advances for the Clinical Genomic Evaluation of Sudden Cardiac Death: Verification of Next-Generation Sequencing Panels for Hereditary Cardiovascular Conditions Using Formalin-Fixed Paraffin-Embedded Tissues and Dried Blood Spots.","authors":"Linnea M Baudhuin,&nbsp;Charles Leduc,&nbsp;Laura J Train,&nbsp;Rajeswari Avula,&nbsp;Michelle L Kluge,&nbsp;Katrina E Kotzer,&nbsp;Peter T Lin,&nbsp;Michael J Ackerman,&nbsp;Joseph J Maleszewski","doi":"10.1161/CIRCGENETICS.117.001844","DOIUrl":"https://doi.org/10.1161/CIRCGENETICS.117.001844","url":null,"abstract":"<p><strong>Background: </strong>Postmortem genetic testing for heritable cardiovascular (CV) disorders is often lacking because ideal specimens (ie, whole blood) are not retained routinely at autopsy. Formalin-fixed paraffin-embedded tissue (FFPET) is ubiquitously collected at autopsy, but DNA quality hampers its use with traditional sequencing methods. Targeted next-generation sequencing may offer the ability to circumvent such limitations, but a method has not been previously described. The primary aim of this study was to develop and evaluate the use of FFPET for heritable CV disorders via next-generation sequencing.</p><p><strong>Methods and results: </strong>Nineteen FFPET (heart) and blood (whole blood or dried blood spot) specimens underwent targeted next-generation sequencing using a custom panel of 101 CV-associated genes. Nucleic acid yield and quality metrics were evaluated in relation to FFPET specimen age (6 months to 15 years; n=14) and specimen type (FFPET versus whole blood and dried blood spot; n=12). Four FFPET cases with a clinical phenotype of heritable CV disorder were analyzed. Accuracy and precision were 100% concordant between all sample types, with read depths >100× for most regions tested. Lower read depth, as low as 40×, was occasionally observed with FFPET and dried blood spot. High-quality DNA was obtained from FFPET samples as old as 15 years. Genomic analysis of FFPET from the 4 phenotype-positive/genotype unknown cases all revealed putative disease-causing variants.</p><p><strong>Conclusions: </strong>Similar performance characteristics were observed for next-generation sequencing of FFPET, whole blood, and dried blood spot in the evaluation of inherited CV disorders. Although blood is preferable for genetic analyses, this study offers an alternative when only FFPET is available.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/CIRCGENETICS.117.001844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35653273","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":"Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).","authors":"Changwei Li, Jiang He, Jing Chen, Jinying Zhao, Dongfeng Gu, James E Hixson, Dabeeru C Rao, Cashell E Jaquish, Treva K Rice, Yun Ju Sung, Tanika N Kelly","doi":"10.1161/CIRCGENETICS.117.001811","DOIUrl":"10.1161/CIRCGENETICS.117.001811","url":null,"abstract":"<p><strong>Background: </strong>Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 <i>df</i> joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity).</p><p><strong>Methods and results: </strong>Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (<i>P</i><1.00×10^-⁴) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 <i>df</i> tests identified interactions for <i>ARL15</i> rs16882447 on systolic BP (<i>P</i>=2.83×10^-9) and <i>RANBP3L</i> rs958929 on pulse pressure (<i>P</i>=1.58×10^-8). The 2 <i>df</i> tests confirmed the <i>ARL15</i> rs16882447 signal for systolic BP (<i>P</i>=1.15×10^-9). Genome-wide gene-based analysis identified <i>CC2D2A</i> (<i>P</i>=2.59×10^-7) at 4p15.32 and <i>BNC2</i> (<i>P</i>=4.49×10^-¹⁰) at 9p22.2 for systolic BP, <i>GGNBP1</i> (<i>P</i>=1.18×10^-⁸), and <i>LINC00336</i> (<i>P</i>=1.36×10^-⁸) at 6p21 for diastolic BP, <i>DAB1</i> (<i>P</i>=1.05×10^-¹³) at 1p32.2, and <i>MIR4466</i> (<i>P</i>=5.34×10^-⁸) at 6q25.3 for pulse pressure. The <i>BNC2</i> (<i>P</i>=3.57×10^-⁸) gene was also significant for mean arterial pressure.</p><p><strong>Conclusions: </strong>We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.</p>","PeriodicalId":10277,"journal":{"name":"Circulation: Cardiovascular Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728702/pdf/nihms921927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9970340","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}