首页 > 最新文献

Circulation: Genomic and Precision Medicine最新文献

英文 中文
Plasma Protein Profiling of Incident Cardiovascular Diseases: A Multisample Evaluation. 血浆蛋白谱分析事件心血管疾病:多样本评估。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-11-28 DOI: 10.1161/CIRCGEN.123.004233
Lars Lind, Olga Titova, Rui Zeng, Daniela Zanetti, Martin Ingelsson, Stefan Gustafsson, Johan Sundström, Johan Ärnlöv, Sölve Elmståhl, Themistocles Assimes, Karl Michaëlsson

Background: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs.

Methods: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure.

Results: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (P<0.0001) in SIMPLER when added to traditional risk factors.

Conclusions: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.

背景:蛋白质组学分析可以潜在地揭示心血管疾病(CVD)的新的病理生理途径,并提高个体水平的预测。因此,我们旨在研究血浆蛋白谱与不同心血管疾病发病率的关系。方法:在4个瑞典前瞻性人群队列(simple[瑞典基于医疗人群的生命过程和环境研究基础设施]、ULSAM(乌普萨拉成年男性纵向研究)、EpiHealth和POEM[肥胖、能量产生和代谢的前瞻性调查])中测量了245种疑似与CVD或代谢相关的血浆蛋白水平,这些队列包括11869名基线无CVD诊断的个体。我们的主要CVD结局是由合并终点定义的,包括心肌梗死、中风或心力衰竭。结果:采用发现/验证方法,在1163名受试者中发现42种蛋白质与我们的主要复合终点相关。在对3种CVD结果的单独荟萃分析中,49种蛋白质与心肌梗死相关,34种与缺血性卒中相关,109种与心力衰竭相关。13种蛋白与所有3种结果相关。其中,尿激酶纤溶酶原激活物表面受体、肾上腺髓质素和KIM-1(肾损伤分子1)在肥胖、能量产生和代谢的前瞻性研究中也与亚临床CVD的几个标志物相关,反映心肌或动脉病变。在预测分析中,对ULSAM中11种蛋白的筛选使CVD的鉴别率提高了3.3%(结论:多个样品的蛋白分析揭示了与随后的心肌梗死、中风和心力衰竭相关的一些新蛋白,提示了这些疾病的共同病理生理途径。KIM-1、尿激酶纤溶酶原激活物表面受体和肾上腺髓质素是CVD新的早期标志物。11个蛋白的选择提高了CVD的识别。
{"title":"Plasma Protein Profiling of Incident Cardiovascular Diseases: A Multisample Evaluation.","authors":"Lars Lind, Olga Titova, Rui Zeng, Daniela Zanetti, Martin Ingelsson, Stefan Gustafsson, Johan Sundström, Johan Ärnlöv, Sölve Elmståhl, Themistocles Assimes, Karl Michaëlsson","doi":"10.1161/CIRCGEN.123.004233","DOIUrl":"10.1161/CIRCGEN.123.004233","url":null,"abstract":"<p><strong>Background: </strong>Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs.</p><p><strong>Methods: </strong>Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure.</p><p><strong>Results: </strong>Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (<i>P</i><0.0001) in SIMPLER when added to traditional risk factors.</p><p><strong>Conclusions: </strong>Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004233"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444118","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}
引用次数: 0
Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research. 心血管疾病知识门户:心血管疾病研究的社区资源。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-10-10 DOI: 10.1161/CIRCGEN.123.004181
Maria C Costanzo, Carolina Roselli, MacKenzie Brandes, Marc Duby, Quy Hoang, Dongkeun Jang, Ryan Koesterer, Parul Kudtarkar, Annie Moriondo, Trang Nguyen, Oliver Ruebenacker, Patrick Smadbeck, Ying Sun, Adam S Butterworth, Krishna G Aragam, R Thomas Lumbers, Amit V Khera, Steven A Lubitz, Patrick T Ellinor, Kyle J Gaulton, Jason Flannick, Noël P Burtt
{"title":"Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.","authors":"Maria C Costanzo, Carolina Roselli, MacKenzie Brandes, Marc Duby, Quy Hoang, Dongkeun Jang, Ryan Koesterer, Parul Kudtarkar, Annie Moriondo, Trang Nguyen, Oliver Ruebenacker, Patrick Smadbeck, Ying Sun, Adam S Butterworth, Krishna G Aragam, R Thomas Lumbers, Amit V Khera, Steven A Lubitz, Patrick T Ellinor, Kyle J Gaulton, Jason Flannick, Noël P Burtt","doi":"10.1161/CIRCGEN.123.004181","DOIUrl":"10.1161/CIRCGEN.123.004181","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004181"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182178","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}
引用次数: 0
Sex Differences in the Association of Genome-Wide Systolic Blood Pressure Polygenic Risk Score With Hypertension. 全基因组收缩压多基因风险评分与高血压相关性的性别差异。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-10-09 DOI: 10.1161/CIRCGEN.123.004259
Naman S Shetty, Akhil Pampana, Nirav Patel, Peng Li, Krishin Yerabolu, Mokshad Gaonkar, Garima Arora, Pankaj Arora
{"title":"Sex Differences in the Association of Genome-Wide Systolic Blood Pressure Polygenic Risk Score With Hypertension.","authors":"Naman S Shetty, Akhil Pampana, Nirav Patel, Peng Li, Krishin Yerabolu, Mokshad Gaonkar, Garima Arora, Pankaj Arora","doi":"10.1161/CIRCGEN.123.004259","DOIUrl":"10.1161/CIRCGEN.123.004259","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004259"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125990","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}
引用次数: 0
Metabolite Signature of Life's Essential 8 and Risk of Coronary Heart Disease Among Low-Income Black and White Americans. 在低收入美国黑人和白人中,生命必需的代谢物特征和冠心病的风险。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-11-28 DOI: 10.1161/CIRCGEN.123.004230
Kui Deng, Deepak K Gupta, Xiao-Ou Shu, Loren Lipworth, Wei Zheng, Victoria E Thomas, Hui Cai, Qiuyin Cai, Thomas J Wang, Danxia Yu

Background: Life's essential 8 (LE8) is a comprehensive construct of cardiovascular health. Yet, little is known about the LE8 score, its metabolic correlates, and their predictive implications among Black Americans and low-income individuals.

Methods: In a nested case-control study of coronary heart disease (CHD) among 299 pairs of Black and 298 pairs of White low-income Americans from the Southern Community Cohort Study, we estimated LE8 score and applied untargeted plasma metabolomics and elastic net with leave-one-out cross-validation to identify metabolite signature (MetaSig) of LE8. Associations of LE8 score and MetaSig with incident CHD were examined using conditional logistic regression. The mediation effect of MetaSig on the LE8-CHD association was also examined. The external validity of MetaSig was evaluated in another nested CHD case-control study among 299 pairs of Chinese adults.

Results: Higher LE8 score was associated with lower CHD risk (standardized odds ratio, 0.61 [95% CI, 0.53-0.69]). The MetaSig, consisting of 133 metabolites, showed significant correlation with LE8 score (r=0.61) and inverse association with CHD (odds ratio, 0.57 [0.49-0.65]), robust to adjustment for LE8 score and across participants with different sociodemographic and health status ([odds ratios, 0.42-0.69]; all P<0.05). MetaSig mediated a large portion of the LE8-CHD association: 53% (32%-80%). Significant associations of MetaSig with LE8 score and CHD risk were found in validation cohort (r=0.49; odds ratio, 0.57 [0.46-0.69]).

Conclusions: Higher LE8 score and its MetaSig were associated with lower CHD risk among low-income Black and White Americans. Metabolomics may offer an objective measure of LE8 and its metabolic phenotype relevant to CHD prevention among diverse populations.

背景:Life's essential 8 (LE8)是心血管健康的综合指标。然而,人们对LE8评分、代谢相关性及其在美国黑人和低收入人群中的预测意义知之甚少。方法:在一项来自南方社区队列研究的299对黑人和298对白人低收入美国人冠心病(CHD)的巢式病例对照研究中,我们估计了LE8评分,并应用非靶向血浆代谢组学和弹性网进行留用交叉验证,以确定LE8的代谢物特征(MetaSig)。采用条件logistic回归检验LE8评分和MetaSig与冠心病事件的关系。MetaSig对LE8-CHD关联的中介作用也进行了研究。MetaSig的外部有效性在另一项包含299对中国成年人的嵌套冠心病病例对照研究中进行了评估。结果:LE8评分越高,冠心病风险越低(标准化优势比为0.61 [95% CI, 0.53-0.69])。由133种代谢物组成的MetaSig与LE8评分呈显著相关(r=0.61),与冠心病呈负相关(比值比为0.57[0.49-0.65]),对LE8评分和不同社会人口统计学和健康状况的参与者进行校正具有稳健性([比值比,0.42-0.69];所有公关= 0.49;优势比为0.57[0.46-0.69])。结论:在低收入美国黑人和白人中,较高的LE8评分及其meta分析与较低的冠心病风险相关。代谢组学可以提供不同人群中与冠心病预防相关的LE8及其代谢表型的客观测量。
{"title":"Metabolite Signature of Life's Essential 8 and Risk of Coronary Heart Disease Among Low-Income Black and White Americans.","authors":"Kui Deng, Deepak K Gupta, Xiao-Ou Shu, Loren Lipworth, Wei Zheng, Victoria E Thomas, Hui Cai, Qiuyin Cai, Thomas J Wang, Danxia Yu","doi":"10.1161/CIRCGEN.123.004230","DOIUrl":"10.1161/CIRCGEN.123.004230","url":null,"abstract":"<p><strong>Background: </strong>Life's essential 8 (LE8) is a comprehensive construct of cardiovascular health. Yet, little is known about the LE8 score, its metabolic correlates, and their predictive implications among Black Americans and low-income individuals.</p><p><strong>Methods: </strong>In a nested case-control study of coronary heart disease (CHD) among 299 pairs of Black and 298 pairs of White low-income Americans from the Southern Community Cohort Study, we estimated LE8 score and applied untargeted plasma metabolomics and elastic net with leave-one-out cross-validation to identify metabolite signature (MetaSig) of LE8. Associations of LE8 score and MetaSig with incident CHD were examined using conditional logistic regression. The mediation effect of MetaSig on the LE8-CHD association was also examined. The external validity of MetaSig was evaluated in another nested CHD case-control study among 299 pairs of Chinese adults.</p><p><strong>Results: </strong>Higher LE8 score was associated with lower CHD risk (standardized odds ratio, 0.61 [95% CI, 0.53-0.69]). The MetaSig, consisting of 133 metabolites, showed significant correlation with LE8 score (<i>r</i>=0.61) and inverse association with CHD (odds ratio, 0.57 [0.49-0.65]), robust to adjustment for LE8 score and across participants with different sociodemographic and health status ([odds ratios, 0.42-0.69]; all <i>P</i><0.05). MetaSig mediated a large portion of the LE8-CHD association: 53% (32%-80%). Significant associations of MetaSig with LE8 score and CHD risk were found in validation cohort (<i>r</i>=0.49; odds ratio, 0.57 [0.46-0.69]).</p><p><strong>Conclusions: </strong>Higher LE8 score and its MetaSig were associated with lower CHD risk among low-income Black and White Americans. Metabolomics may offer an objective measure of LE8 and its metabolic phenotype relevant to CHD prevention among diverse populations.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004230"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444117","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}
引用次数: 0
Potential Diagnostic Role for a Combined Postmortem DNA and RNA Sequencing for Brugada Syndrome. 死后DNA和RNA测序对Brugada综合征的潜在诊断作用。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-10-05 DOI: 10.1161/CIRCGEN.122.004251
Carlos Bueno-Beti, David C Johnson, Chris Miles, Joseph Westaby, Mary N Sheppard, Elijah R Behr, Angeliki Asimaki
{"title":"Potential Diagnostic Role for a Combined Postmortem DNA and RNA Sequencing for Brugada Syndrome.","authors":"Carlos Bueno-Beti, David C Johnson, Chris Miles, Joseph Westaby, Mary N Sheppard, Elijah R Behr, Angeliki Asimaki","doi":"10.1161/CIRCGEN.122.004251","DOIUrl":"10.1161/CIRCGEN.122.004251","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004251"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112761","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}
引用次数: 0
Genotype-Phenotype Taxonomy of Hypertrophic Cardiomyopathy. 肥厚性心肌病的基因型-表型分类。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-11-28 DOI: 10.1161/CIRCGEN.123.004200
Lara Curran, Antonio de Marvao, Paolo Inglese, Kathryn A McGurk, Pierre-Raphaël Schiratti, Adam Clement, Sean L Zheng, Surui Li, Chee Jian Pua, Mit Shah, Mina Jafari, Pantazis Theotokis, Rachel J Buchan, Sean J Jurgens, Claire E Raphael, Arun John Baksi, Antonis Pantazis, Brian P Halliday, Dudley J Pennell, Wenjia Bai, Calvin W L Chin, Rafik Tadros, Connie R Bezzina, Hugh Watkins, Stuart A Cook, Sanjay K Prasad, James S Ware, Declan P O'Regan

Background: Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.

Methods: We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.

Results: Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96]; P<0.002). Four main phenotypic branches were identified using unsupervised learning of 3-dimensional shape: (1) nonsarcomeric hypertrophy with coexisting hypertension; (2) diffuse and basal asymmetrical hypertrophy associated with outflow tract obstruction; (3) isolated basal hypertrophy; and (4) milder nonobstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for pathogenic or likely pathogenic variants, 2.18 [95% CI, 1.93-2.28]; P=0.0001). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalizable to an independent cohort (trustworthiness, M1: 0.86-0.88).

Conclusions: We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.

背景:肥厚性心肌病(HCM)是与异质性表型相关的心源性猝死的重要原因,但目前尚无系统的形态学分类或相关风险评估框架。在这里,我们定量调查了HCM中的基因型-表型关联,以获得疾病表达的数据驱动分类。方法:我们招募了436例HCM患者(中位年龄60岁;28.8%女性),有临床、遗传和影像学资料。来自新加坡的60例HCM患者的独立队列研究(中位年龄59岁;11%女性)和参考人群来自UK Biobank (n= 16691;平均年龄55岁;52.5%的女性)也被招募。我们利用机器学习分析了心脏磁共振成像左心室的三维结构,并建立了基于树的HCM表型分类。基因型和死亡风险分布被预测到树上。结果:与基因型阴性个体相比,HCM致病性或可能致病性变异携带者左心室体积较小,但基底间隔肥大较大,寿命缩短(平均随访时间9.9年)(风险比2.66 [95% CI, 1.42-4.96];页= 0.0001)。HCM的多基因风险也与不同的疾病表达模式和程度有关。该模型可推广到一个独立的队列(可信度,M1: 0.86-0.88)。结论:我们报告了一种数据驱动的HCM分类方法,用于识别具有相似形态学的患者群体,同时保留疾病严重程度、遗传风险和结果的连续性。这种方法将有助于理解疾病多样性的原因和后果。
{"title":"Genotype-Phenotype Taxonomy of Hypertrophic Cardiomyopathy.","authors":"Lara Curran, Antonio de Marvao, Paolo Inglese, Kathryn A McGurk, Pierre-Raphaël Schiratti, Adam Clement, Sean L Zheng, Surui Li, Chee Jian Pua, Mit Shah, Mina Jafari, Pantazis Theotokis, Rachel J Buchan, Sean J Jurgens, Claire E Raphael, Arun John Baksi, Antonis Pantazis, Brian P Halliday, Dudley J Pennell, Wenjia Bai, Calvin W L Chin, Rafik Tadros, Connie R Bezzina, Hugh Watkins, Stuart A Cook, Sanjay K Prasad, James S Ware, Declan P O'Regan","doi":"10.1161/CIRCGEN.123.004200","DOIUrl":"10.1161/CIRCGEN.123.004200","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.</p><p><strong>Methods: </strong>We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.</p><p><strong>Results: </strong>Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96]; <i>P</i><0.002). Four main phenotypic branches were identified using unsupervised learning of 3-dimensional shape: (1) nonsarcomeric hypertrophy with coexisting hypertension; (2) diffuse and basal asymmetrical hypertrophy associated with outflow tract obstruction; (3) isolated basal hypertrophy; and (4) milder nonobstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for pathogenic or likely pathogenic variants, 2.18 [95% CI, 1.93-2.28]; <i>P</i>=0.0001). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalizable to an independent cohort (trustworthiness, M<sub>1</sub>: 0.86-0.88).</p><p><strong>Conclusions: </strong>We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004200"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444116","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}
引用次数: 0
Compound Heterozygous Truncating Variants in the BAG5 Gene As a Cause of Early-Onset Dilated Cardiomyopathy. BAG5基因中的复合杂合子截短变体是早期发病的扩张型心肌病的原因。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-10-24 DOI: 10.1161/CIRCGEN.123.004282
Shunsuke Inoue, Toshiyuki Ko, Seitaro Nomura, Takanobu Yamada, Bo Zhang, Zhehao Dai, Takahiro Jimba, Manami Katoh, Junichi Ishida, Eisuke Amiya, Masaru Hatano, Norifumi Takeda, Hiroyuki Morita, Minoru Ono, Issei Komuro
{"title":"Compound Heterozygous Truncating Variants in the <i>BAG5</i> Gene As a Cause of Early-Onset Dilated Cardiomyopathy.","authors":"Shunsuke Inoue, Toshiyuki Ko, Seitaro Nomura, Takanobu Yamada, Bo Zhang, Zhehao Dai, Takahiro Jimba, Manami Katoh, Junichi Ishida, Eisuke Amiya, Masaru Hatano, Norifumi Takeda, Hiroyuki Morita, Minoru Ono, Issei Komuro","doi":"10.1161/CIRCGEN.123.004282","DOIUrl":"10.1161/CIRCGEN.123.004282","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004282"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688958","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}
引用次数: 0
Hypertrophic Cardiomyopathy Secondary to RAF1 Cysteine-Rich Domain Variants. RAF1富含半胱氨酸结构域变体继发的肥厚性心肌病。
IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1161/CIRCGEN.123.004262
Dominic E Fullenkamp, Ryan M Jorgensen, Desiree F Leach, Arjun Sinha, Isabella M Salamone, Jamie R Johnston, Lisa M Dellefave-Castillo, Lubna Choudhury, Elizabeth M McNally, Lisa D Wilsbacher
{"title":"Hypertrophic Cardiomyopathy Secondary to <i>RAF1</i> Cysteine-Rich Domain Variants.","authors":"Dominic E Fullenkamp, Ryan M Jorgensen, Desiree F Leach, Arjun Sinha, Isabella M Salamone, Jamie R Johnston, Lisa M Dellefave-Castillo, Lubna Choudhury, Elizabeth M McNally, Lisa D Wilsbacher","doi":"10.1161/CIRCGEN.123.004262","DOIUrl":"10.1161/CIRCGEN.123.004262","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"e004262"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410959","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}
引用次数: 0
Combining Polygenic and Proteomic Risk Scores With Clinical Risk Factors to Improve Performance for Diagnosing Absence of Coronary Artery Disease in Patients With de novo Chest Pain. 将多基因和蛋白质组风险评分与临床风险因素相结合,提高诊断新发胸痛患者无冠状动脉疾病的能力。
IF 7.4 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-10-01 Epub Date: 2023-09-27 DOI: 10.1161/CIRCGEN.123.004053
Peter Loof Møller, Palle Duun Rohde, Jonathan Nørtoft Dahl, Laust Dupont Rasmussen, Samuel Emil Schmidt, Louise Nissen, Victoria McGilligan, Jacob F Bentzon, Daniel F Gudbjartsson, Kari Stefansson, Hilma Holm, Simon Winther, Morten Bøttcher, Mette Nyegaard

Background: Patients with de novo chest pain, referred for evaluation of possible coronary artery disease (CAD), frequently have an absence of CAD resulting in millions of tests not having any clinical impact. The objective of this study was to investigate whether polygenic risk scores and targeted proteomics improve the prediction of absence of CAD in patients with suspected CAD, when added to the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS).

Methods: Genotyping and targeted plasma proteomics (N=368 proteins) were performed in 1440 patients with symptoms suspected to be caused by CAD undergoing coronary computed tomography angiography. Based on individual genotypes, a polygenic risk score for CAD (PRSCAD) was calculated. The prediction was performed using combinations of PRSCAD, proteins, and PMRS as features in models using stability selection and machine learning.

Results: Prediction of absence of CAD yielded an area under the curve of PRSCAD-model, 0.64±0.03; proteomic-model, 0.58±0.03; and PMRS model, 0.76±0.02. No significant correlation was found between the genetic and proteomic risk scores (Pearson correlation coefficient, -0.04; P=0.13). Optimal predictive ability was achieved by the full model (PRSCAD+protein+PMRS) yielding an area under the curve of 0.80±0.02 for absence of CAD, significantly better than the PMRS model alone (P<0.001). For reclassification purpose, the full model enabled down-classification of 49% (324 of 661) of the 5% to 15% pretest probability patients and 18% (113 of 611) of >15% pretest probability patients.

Conclusions: For patients with chest pain and low-intermediate CAD risk, incorporating targeted proteomics and polygenic risk scores into the risk assessment substantially improved the ability to predict the absence of CAD. Genetics and proteomics seem to add complementary information to the clinical risk factors and improve risk stratification in this large patient group.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT02264717.

背景:被转诊评估可能的冠状动脉疾病(CAD)的新发胸痛患者经常没有CAD,导致数百万次检测没有任何临床影响。本研究的目的是研究多基因风险评分和靶向蛋白质组学是否能改善疑似CAD患者无CAD的预测,将其添加到PROMISE(用于评估胸痛的前瞻性多中心成像研究)最低风险评分(PMRS)中。方法:对1440名接受冠状动脉计算机断层扫描血管造影术的疑似CAD症状患者进行基因分型和靶向血浆蛋白质组学(N=368种蛋白质)。根据个体基因型,计算CAD的多基因风险评分(PRSCAD)。在使用稳定性选择和机器学习的模型中,使用PRSCAD、蛋白质和PMRS的组合作为特征进行预测。结果:预测无CAD时,PRSCAD模型的曲线下面积为0.64±0.03;蛋白质组学模型,0.58±0.03;PMRS模型为0.76±0.02。遗传和蛋白质组学风险评分之间没有发现显著的相关性(Pearson相关系数,-0.04;P=0.013)。全模型(PRSCAD+蛋白质+PMRS)在没有CAD的情况下产生0.80±0.02的曲线下面积,实现了最佳的预测能力,明显优于单独的PMRS模型(P15%的预测概率患者。结论:对于胸痛和中低度CAD风险的患者,将靶向蛋白质组学和多基因风险评分纳入风险评估大大提高了预测无CAD的能力。遗传学和蛋白质组学似乎为临床风险因素增加了补充信息,并改善了这一大样本的风险分层ient组。注册:URL:https://www.Clinicaltrials:政府;唯一标识符:NCT02264717。
{"title":"Combining Polygenic and Proteomic Risk Scores With Clinical Risk Factors to Improve Performance for Diagnosing Absence of Coronary Artery Disease in Patients With de novo Chest Pain.","authors":"Peter Loof Møller,&nbsp;Palle Duun Rohde,&nbsp;Jonathan Nørtoft Dahl,&nbsp;Laust Dupont Rasmussen,&nbsp;Samuel Emil Schmidt,&nbsp;Louise Nissen,&nbsp;Victoria McGilligan,&nbsp;Jacob F Bentzon,&nbsp;Daniel F Gudbjartsson,&nbsp;Kari Stefansson,&nbsp;Hilma Holm,&nbsp;Simon Winther,&nbsp;Morten Bøttcher,&nbsp;Mette Nyegaard","doi":"10.1161/CIRCGEN.123.004053","DOIUrl":"10.1161/CIRCGEN.123.004053","url":null,"abstract":"<p><strong>Background: </strong>Patients with de novo chest pain, referred for evaluation of possible coronary artery disease (CAD), frequently have an absence of CAD resulting in millions of tests not having any clinical impact. The objective of this study was to investigate whether polygenic risk scores and targeted proteomics improve the prediction of absence of CAD in patients with suspected CAD, when added to the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk score (PMRS).</p><p><strong>Methods: </strong>Genotyping and targeted plasma proteomics (N=368 proteins) were performed in 1440 patients with symptoms suspected to be caused by CAD undergoing coronary computed tomography angiography. Based on individual genotypes, a polygenic risk score for CAD (PRS<sub>CAD</sub>) was calculated. The prediction was performed using combinations of PRS<sub>CAD</sub>, proteins, and PMRS as features in models using stability selection and machine learning.</p><p><strong>Results: </strong>Prediction of absence of CAD yielded an area under the curve of PRS<sub>CAD</sub>-model, 0.64±0.03; proteomic-model, 0.58±0.03; and PMRS model, 0.76±0.02. No significant correlation was found between the genetic and proteomic risk scores (Pearson correlation coefficient, -0.04; <i>P</i>=0.13). Optimal predictive ability was achieved by the full model (PRS<sub>CAD</sub>+protein+PMRS) yielding an area under the curve of 0.80±0.02 for absence of CAD, significantly better than the PMRS model alone (<i>P</i><0.001). For reclassification purpose, the full model enabled down-classification of 49% (324 of 661) of the 5% to 15% pretest probability patients and 18% (113 of 611) of >15% pretest probability patients.</p><p><strong>Conclusions: </strong>For patients with chest pain and low-intermediate CAD risk, incorporating targeted proteomics and polygenic risk scores into the risk assessment substantially improved the ability to predict the absence of CAD. Genetics and proteomics seem to add complementary information to the clinical risk factors and improve risk stratification in this large patient group.</p><p><strong>Registration: </strong>URL: https://www.</p><p><strong>Clinicaltrials: </strong>gov; Unique identifier: NCT02264717.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"442-451"},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41117441","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}
引用次数: 0
Novel Insights Into DMD-Associated Dilated Cardiomyopathy. DMD相关扩张型心肌病的新见解。
IF 7.4 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2023-10-01 Epub Date: 2023-09-27 DOI: 10.1161/CIRCGEN.123.004384
Teresa Wang, Jessica Chowns, Sharlene M Day
{"title":"Novel Insights Into DMD-Associated Dilated Cardiomyopathy.","authors":"Teresa Wang,&nbsp;Jessica Chowns,&nbsp;Sharlene M Day","doi":"10.1161/CIRCGEN.123.004384","DOIUrl":"10.1161/CIRCGEN.123.004384","url":null,"abstract":"","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":" ","pages":"431-433"},"PeriodicalIF":7.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113673","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}
引用次数: 0
期刊
Circulation: Genomic and Precision Medicine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1