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Cardiovascular genomic

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https://www.readbyqxmd.com/read/28334273/gwas-summary-based-pathway-analysis-correcting-for-the-genetic-confounding-impact-of-environmental-exposures
#1
Qianrui Fan, Feng Zhang, Wenyu Wang, Jiawen Xu, Jingcan Hao, Awen He, Yan Wen, Ping Li, Xiao Liang, Yanan Du, Li Liu, Cuiyan Wu, Sen Wang, Xi Wang, Yujie Ning, Xiong Guo
Genome-wide association study (GWAS)-based pathway association analysis is a powerful approach for the genetic studies of human complex diseases. However, the genetic confounding effects of environment exposure-related genes can decrease the accuracy of GWAS-based pathway association analysis of target diseases. In this study, we developed a pathway association analysis approach, named Mendelian randomization-based pathway enrichment analysis (MRPEA), which was capable of correcting the genetic confounding effects of environmental exposures, using the GWAS summary data of environmental exposures...
March 8, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28333714/novel-regulators-of-plasma-lipid-levels
#2
Natalia Loaiza, Federico Oldoni, Jan A Kuivenhoven
PURPOSE OF REVIEW: To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism. RECENT FINDINGS: Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93" and "Wiskott-Aldrich syndrome protein and SCAR homologue" complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway...
March 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28330812/molecular-evidence-for-differential-long-term-outcomes-of-early-life-severe-acute-malnutrition
#3
Allan Sheppard, Sherry Ngo, Xiaoling Li, Michael Boyne, Debbie Thompson, Anthony Pleasants, Peter Gluckman, Terrence Forrester
BACKGROUND: Severe acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences...
March 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28329165/four-genome-wide-association-studies-identify-new-extreme-longevity-variants
#4
Paola Sebastiani, Anastasia Gurinovich, Harold Bae, Stacy Andersen, Alberto Malovini, Gil Atzmon, Francesco Villa, Aldi T Kraja, Danny Ben-Avraham, Nir Barzilai, Annibale Puca, Thomas T Perls
The search for the genetic determinants of extreme human longevity has been challenged by the phenotype's rarity and its nonspecific definition by investigators. To address these issues, we established a consortium of four studies of extreme longevity that contributed 2,070 individuals who survived to the oldest one percentile of survival for the 1900 U.S. birth year cohort. We conducted various analyses to discover longevity-associated variants (LAV) and characterized those LAVs that differentiate survival to extreme age at death (eSAVs) from those LAVs that become more frequent in centenarians because of mortality selection (eg, survival to younger years)...
March 15, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28329018/a-unique-microrna-profile-in-end-stage-heart-failure-indicates-alterations-in-specific-cardiovascular-signaling-networks
#5
Sathyamangla V Naga Prasad, Manveen K Gupta, Zhong-Hui Duan, Venkata Suresh K Surampudi, Chang-Gong Liu, Ashwin Kotwal, Christine S Moravec, Randall C Starling, Dianne M Perez, Subha Sen, Qingyu Wu, Edward F Plow, Sadashiva Karnik
It is well established that the gene expression patterns are substantially altered in cardiac hypertrophy and heart failure, however, less is known about the reasons behind such global differences. MicroRNAs (miRNAs) are short non-coding RNAs that can target multiple molecules to regulate wide array of proteins in diverse pathways. The goal of the study was to profile alterations in miRNA expression using end-stage human heart failure samples with an aim to build signaling network pathways using predicted targets for the altered miRNA and to determine nodal molecules regulating individual networks...
2017: PloS One
https://www.readbyqxmd.com/read/28326484/genome-wide-transcriptional-analysis-of-cardiovascular-related-genes-and-pathways-induced-by-pm2-5-in-human-myocardial-cells
#6
Lin Feng, Xiaozhe Yang, Collins Otieno Asweto, Jing Wu, Yannan Zhang, Hejing Hu, Yanfeng Shi, Junchao Duan, Zhiwei Sun
Air pollution has been a major environment-related health threat. Most of the studies on PM2.5 toxicity have verified on the cardiovascular system and endothelial cells. However, researches on PM2.5-induced myocardial-related toxicity are limited. This study aims to fully understand the toxic effects of PM2.5 on human myocardial cell (AC16) and explore its molecular mechanism based on microarray analysis and bioinformatics analysis. Microarray data analysis manifested that PM2.5-induced toxicity affected expression of 472 genes compared with the control group, including 166 upregulated genes and 306 downregulated genes in human myocardial (AC16) cells...
March 22, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28325553/metabolomics-through-the-lens-of-precision-cardiovascular-medicine
#7
REVIEW
Sin Man Lam, Yuan Wang, Bowen Li, Jie Du, Guanghou Shui
Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development...
March 8, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28323875/the-clinical-features-outcomes-and-genetic-characteristics-of-hypertrophic-cardiomyopathy-patients-with-severe-right-ventricular-hypertrophy
#8
Xiying Guo, Chaomei Fan, Lei Tian, Yanling Liu, Hongyue Wang, Shihua Zhao, Fujian Duan, Xiuling Zhang, Xing Zhao, Fengqi Wang, Hongguang Zhu, Aiqing Lin, Xia Wu, Yishi Li
INTRODUCTION: Severe right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH. METHODS: HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH...
2017: PloS One
https://www.readbyqxmd.com/read/28320757/additional-candidate-genes-for-human-atherosclerotic-disease-identified-through-annotation-based-on-chromatin-organization
#9
Saskia Haitjema, Claartje A Meddens, Sander W van der Laan, Daniel Kofink, Magdalena Harakalova, Vinicius Tragante, Hassan Foroughi Asl, Jessica van Setten, Maarten M Brandt, Joshua C Bis, Christopher O'Donnell, Caroline Cheng, Imo E Hoefer, Johannes Waltenberger, Erik Biessen, J Wouter Jukema, Pieter A F M Doevendans, Edward E S Nieuwenhuis, Jeanette Erdmann, Johan L M Björkegren, Gerard Pasterkamp, Folkert W Asselbergs, Hester M den Ruijter, Michal Mokry
BACKGROUND: As genome-wide association efforts, such as CARDIoGRAM and METASTROKE, are ongoing to reveal susceptibility loci for their underlying disease-atherosclerotic disease-identification of candidate genes explaining the associations of these loci has proven the main challenge. Many disease susceptibility loci colocalize with DNA regulatory elements, which influence gene expression through chromatin interactions. Therefore, the target genes of these regulatory elements can be considered candidate genes...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28302752/lower-circulating-folate-induced-by-a-fidgetin-intronic-variant-is-associated-with-reduced-congenital-heart-disease-susceptibility
#10
Dan Wang, Feng Wang, Kai-Hu Shi, Hui Tao, Yang Li, Rui Zhao, Han Lu, Wenyuan Duan, Bin Qiao, Shi-Min Zhao, Hongyan Wang, Jian-Yuan Zhao
Background -Folate deficiency is an independent risk factor for congenital heart disease (CHD); however, the maternal plasma folate level is paradoxically not a good diagnostic marker. Genome-wide surveys have identified variants of non-folate metabolic genes associated with the plasma folate level, suggesting that these genetic polymorphisms are potential risk factors for CHD. Methods -To examine the effects of folate concentration-related variations on CHD risk in the Han Chinese population, we performed three independent case-control studies including a total of 1,489 CHD patients and 1,745 controls...
March 16, 2017: Circulation
https://www.readbyqxmd.com/read/28302552/exploring-overlaps-between-the-genomic-and-environmental-determinants-of-lvh-and-stroke-a-multicenter-study-in-west-africa
#11
Abiodun M Adeoye, Bruce Ovbiagele, Philip Kolo, Lambert Appiah, Akinyemi Aje, Oladimeji Adebayo, Fred Sarfo, Joshua Akinyemi, Gregory Adekunle, Francis Agyekum, Vincent Shidali, Okechukwu Ogah, Dan Lackland, Mulugeta Gebregziabher, Donna Arnett, Hemant K Tiwari, Rufus Akinyemi, Ojo Olakanmi Olagoke, Ayodipupo Sikiru Oguntade, Taiwo Olunuga, Kelechi Uwanruochi, Carolyn Jenkins, Patrick Adadey, Henry Iheonye, Lukman Owolabi, Reginald Obiako, Samuel Akinjopo, Kevin Armstrong, Albert Akpalu, Adekunle Fakunle, Raelle Saulson, Mayowa Aridegbe, Paul Olowoyo, Godwin Osaigbovo, Josephine Akpalu, Bimbo Fawale, Philip Adebayo, Oyedunni Arulogun, Philip Ibinaiye, Atinuke Agunloye, Naser Ishaq, Kolawole Wahab, Onoja Akpa, Omisore Adeleye, Andrew Bock-Oruma, Godwin Ogbole, Sylvia Melikam, Joseph Yaria, Luqman Ogunjimi, Abdul Salaam, Taofiki Sunmonu, Akintomiwa Makanjuola, Temitope Farombi, Ruth Laryea, Ezinne Uvere, Salaam Kehinde, Innocent Chukwuonye, Paschal Azuh, Morenikeji Komolafe, Adeseye Akintunde, Olugbo Obiabo, Olusegun Areo, Issa Kehinde, Adeniyi G Amusa, Mayowa Owolabi
BACKGROUND: Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown. OBJECTIVES: We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study. METHODS: SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria...
March 13, 2017: Global Heart
https://www.readbyqxmd.com/read/28298470/genetically-driven-hyperglycemia-increases-risk-of-coronary-artery-disease-separately-from-type-2-diabetes
#12
Jordi Merino, Aaron Leong, Daniel C Posner, Bianca Porneala, Lluís Masana, Josée Dupuis, Jose C Florez
OBJECTIVE: This study tested the hypothesis that genetically raised hyperglycemia increases coronary artery disease (CAD) risk separately from the risk conferred by type 2 diabetes as a whole. RESEARCH DESIGN AND METHODS: We conducted a Mendelian randomization (MR) analysis using summary-level statistics from the largest published meta-analyses of genome-wide association studies (GWAS) for fasting glucose (FG) (n = 133,010 participants free of diabetes) and CAD (n = 63,746 case subjects and 130,681 control subjects) of predominantly European ancestry...
March 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28298293/discovery-and-fine-mapping-of-loci-associated-with-monounsaturated-fatty-acids-through-trans-ethnic-meta-analysis-in-chinese-and-european-populations
#13
Yao Hu, Toshiko Tanaka, Jingwen Zhu, Weihua Guan, Jason H Y Wu, Bruce M Psaty, Barbara McKnight, Irena B King, Qi Sun, Melissa Richard, Ani Manichaikul, Alexis C Frazier-Wood, Edmond K Kabagambe, Paul N Hopkins, Jose M Ordovas, Luigi Ferrucci, Stefania Bandinelli, Donna K Arnett, Yii-Der I Chen, Shuang Liang, David S Siscovick, Michael Y Tsai, Stephen S Rich, Myriam Fornage, Frank B Hu, Eric B Rimm, Majken K Jensen, Rozenn N Lemaitre, Dariush Mozaffarian, Lyn M Steffen, Andrew P Morris, Huaixing Li, Xu Lin
Monounsaturated fatty acids (MUFAs) are unsaturated fatty acids with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels were associated with cardiometabolic disorders including cardiovascular disease (CVD), type 2 diabetes (T2D) and metabolic syndrome (MS). Previous genome-wide association studies (GWAS) have identified seven loci for plasma and erythrocyte palmitoleic acid and oleic acid levels in populations of European origin...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28292297/subclinical-left-ventricular-diastolic-dysfunction-and-incident-type-2-diabetes-risk-the-korean-genome-and-epidemiology-study
#14
Juri Park, Jin-Seok Kim, Seong Hwan Kim, Sunwon Kim, Sang Yup Lim, Hong-Euy Lim, Goo-Yeong Cho, Ki-Chul Sung, Jang-Young Kim, Inkyung Baik, Kwang Kon Koh, Jung Bok Lee, Seung Ku Lee, Chol Shin
BACKGROUND: Subclinical left ventricular (LV) diastolic dysfunction in type 2 diabetes (T2D) is a common finding and represents an early sign of diabetic cardiomyopathy. However, the relationship between LV diastolic dysfunction and the incident T2D has not been previously studied. METHODS: A total of 1817 non-diabetic participants (mean age, 54 years; 48% men) from the Korean Genome and Epidemiology Study who were free of cardiovascular disease were studied. LV structure and function were assessed by conventional echocardiography and tissue Doppler imaging...
March 14, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28289683/multidimensional-integrative-genomics-approaches-to-dissecting-cardiovascular-disease
#15
REVIEW
Douglas Arneson, Le Shu, Brandon Tsai, Rio Barrere-Cain, Christine Sun, Xia Yang
Elucidating the mechanisms of complex diseases such as cardiovascular disease (CVD) remains a significant challenge due to multidimensional alterations at molecular, cellular, tissue, and organ levels. To better understand CVD and offer insights into the underlying mechanisms and potential therapeutic strategies, data from multiple omics types (genomics, epigenomics, transcriptomics, metabolomics, proteomics, microbiomics) from both humans and model organisms have become available. However, individual omics data types capture only a fraction of the molecular mechanisms...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28287809/increased-risk-of-chd-in-the-presence-of-rs7865618-a-allele-tehran-lipid-and-glucose-study
#16
Samaneh Matoo, Mohammad Sadegh Fallah, Maryam Sadat Daneshpour, Reyhaneh Mousavi, Bahareh Sedaghati Khayat, Mandana Hasanzad, Fereidoun Azizi
BACKGROUND: Recent genome-wide association studies (GWAS) in European populations have indicated that the rs12526453 polymorphism located in phosphatase and actin regulator 1 gene (PHACTR1), mapping to chromosome 6p24 and rs7865618 polymorphism in the cyclin-dependent kinase inhibitor B antisense RNA 1 gene (CDKN2B-AS1) on 9p21.3 are associated with coronary heart disease (CHD). This study was carried out to investigate the association of these polymorphisms and CHD in an Iranian population...
March 2017: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/28286759/bioinformatics-analysis-reveals-micrornas-regulating-biological-pathways-in-exercise-induced-cardiac-physiological-hypertrophy
#17
REVIEW
Jiahong Xu, Yang Liu, Yuan Xie, Cuimei Zhao, Hongbao Wang
Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28284844/investigating-methotrexate-toxicity-within-a-randomized-double-blinded-placebo-controlled-trial-rationale-and-design-of-the-cardiovascular-inflammation-reduction-trial-adverse-events-cirt-ae-study
#18
Jeffrey A Sparks, Medha Barbhaiya, Elizabeth W Karlson, Susan Y Ritter, Soumya Raychaudhuri, Cassandra C Corrigan, Fengxin Lu, Jacob Selhub, Daniel I Chasman, Nina P Paynter, Paul M Ridker, Daniel H Solomon
BACKGROUND: The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease...
February 10, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28283927/a-review-of-the-genetics-of-hypertension-with-a-focus-on-gene-environment-interactions
#19
REVIEW
R J Waken, Lisa de Las Fuentes, D C Rao
PURPOSE OF REVIEW: Here, we discuss the interpretation and modeling of gene-environment interactions in hypertension-related phenotypes, with a focus on the necessary assumptions and possible challenges. RECENT FINDINGS: Recently, small cohort studies have discovered several novel genetic variants associated with hypertension-related phenotypes through modeling gene-environment interactions. Several consortia-based meta-analytic efforts have uncovered many novel genetic variants in hypertension without modeling interaction terms, giving promise to future meta-analytic efforts that incorporate gene-environment interactions...
March 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28279970/serum-sortilin-associates-with-aortic-calcification-and-cardiovascular-risk-in-men
#20
Claudia Goettsch, Hiroshi Iwata, Joshua D Hutcheson, Christopher J O'Donnell, Roland Chapurlat, Nancy R Cook, Masanori Aikawa, Pawel Szulc, Elena Aikawa
OBJECTIVE: Genome-wide association studies and preclinical studies demonstrated a role of sortilin in lipid metabolism, inflammation, and vascular calcification-all cardiovascular risk factors. We evaluated the association of serum sortilin levels with the risk of major adverse cerebrovascular and cardiovascular events (MACCE) and the severity of abdominal aortic calcification (AAC). APPROACH AND RESULTS: A cohort of community-dwelling men aged ≥50 years (n=830) was assessed...
March 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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