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https://www.readbyqxmd.com/read/30334629/vascular-biology-of-superoxide-generating-nadph-oxidase-5-nox5-implications-in-hypertension-and-cardiovascular-disease
#1
Rhian M Touyz, Aikaterini Anagnostopoulou, Livia Camargo, Francisco Rios, Augusto Montezano
SIGNIFICANCE:  NADPH oxidases (Nox) of which there are 7 isoforms (Nox1-5, Duox1/Duox2) are professional oxidases functioning as ROS-generating enzymes. ROS are signaling molecules important in physiological processes. Increased ROS production and altered redox signaling in the vascular system have been implicated in the pathophysiology of cardiovascular diseases, including hypertension, and have been attributed, in part, to increased Nox activity. RECENT ADVANCES:  Nox1,2,4,5 are expressed and functionally active in human vascular cells...
October 18, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/30281215/ccl21-as-a-potential-biomarker-for-pulmonary-arterial-hypertension-in-systemic-sclerosis
#2
Anna-Maria Hoffmann-Vold, Øyvind Molberg
We thank Zhou and co-workers for their interest regarding our newly published manuscript on the role of CCL21 in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). Here, we want to respond to their concerns. Genome-wide association studies (GWASs) have been foreshadowed to be a major advance in biomedical discovery, with many robust associations to complex diseases. However, although there are found polymorphisms with SSc, there are, to date, no existing genetic loci for SSc-PAH...
October 3, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/30211179/hypertension-genomics-and-cardiovascular-prevention
#3
REVIEW
Fu Liang Ng, Helen R Warren, Mark J Caulfield
Hypertension continues to be a major risk factor for global mortality, and recent genome-wide association studies (GWAS) have expanded in size, leading to the identification of further genetic loci influencing blood pressure. In light of the new knowledge from the largest cardiovascular GWAS to date, we review the potential impact of genomics on discovering potential drug targets, risk stratification with genetic risk scores, drug selection with pharmacogenetics, and exploring insights provided by gene-environment interactions...
August 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/30149742/a-gwas-supported-variant-interacting-with-diabetes-predicts-risk-of-atherothrombotic-stroke-in-han-chinese-population
#4
Zibao Li, Bo Sun, Mengmeng Gu, Mengmeng Wang, Xi Cheng, Jia Lv, Si Cen, Shuai Zhang, Zhengze Dai, Yongjie Bai, Shun Li, Guiling Wang, Zhiqiang Weng, Yonghui Shi, Zhizhong Zhang, Xinfeng Liu
BACKGROUND: A recent genome-wide association study (GWAS) has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. METHODS: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS...
August 28, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/30146708/association-of-genetic-risk-score-and-chronic-kidney-disease-in-a-japanese-population
#5
Ryosuke Fujii, Asahi Hishida, Masahiro Nakatochi, Norihiro Furusyo, Masayuki Murata, Keitaro Tanaka, Chisato Shimanoe, Sadao Suzuki, Miki Watanabe, Nagato Kuriyama, Teruhide Koyama, Toshiro Takezaki, Ippei Shimoshikiryo, Kokichi Arisawa, Sakurako Katsuura-Kamano, Naoyuki Takashima, Tanvir C Turin, Kiyonori Kuriki, Kaori Endoh, Haruo Mikami, Yohko Nakamura, Isao Oze, Hidemi Ito, Michiaki Kubo, Yukihide Momozawa, Takaaki Kondo, Mariko Naito, Kenji Wakai
Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies (GWAS) have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11,283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort (J-MICC) Study sites...
August 26, 2018: Nephrology
https://www.readbyqxmd.com/read/30137437/in-silico-drug-screening-by-using-genome-wide-association-study-data-repurposed-dabrafenib-an-anti-melanoma-drug-for-parkinson-s-disease
#6
Takeshi Uenaka, Wataru Satake, Pei-Chieng Cha, Hideki Hayakawa, Kousuke Baba, Shiying Jiang, Kazuhiro Kobayashi, Motoi Kanagawa, Yukinori Okada, Hideki Mochizuki, Tatsushi Toda
Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss. At present, there are no drugs that stop the progression of PD. As with other multifactorial genetic disorders, genome-wide association studies (GWASs) found multiple risk loci for PD, although their clinical significance remains uncertain. Here, we report the identification of candidate drugs for PD by a method using GWAS data and in silico databases. We identified 57 Food and Drug Administration-approved drug families as candidate neuroprotective drugs for PD...
August 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/30110940/pervasive-modulation-of-obesity-risk-by-the-environment-and-genomic-background
#7
Sini Nagpal, Greg Gibson, Urko M Marigorta
The prevalence of the so-called diseases of affluence, such as type 2 diabetes or hypertension, has increased dramatically in the last two generations. Although genome-wide association studies (GWAS) have discovered hundreds of genes involved in disease etiology, the sudden increase in disease incidence suggests a major role for environmental risk factors. Obesity constitutes a case example of a modern trait shaped by contemporary environment, although with considerable debates about the extent to which gene-by-environment (G×E) interactions accentuate obesity risk in individuals following obesogenic lifestyles...
August 14, 2018: Genes
https://www.readbyqxmd.com/read/30022276/genetics-of-coronary-artery-disease-in-the-light-of-genome-wide-association-studies
#8
REVIEW
Heribert Schunkert, Moritz von Scheidt, Thorsten Kessler, Barbara Stiller, Lingyao Zeng, Baiba Vilne
As clinicians, we understand the development of atherosclerosis as a consequence of cholesterol deposition and inflammation in the arterial wall, both being triggered by traditional risk factors such as hypertension, hyperlipidaemia or diabetes mellitus. Another risk factor is genetic predisposition, as indicated by the predictive value of a positive family history. However, we had to wait until recently to appreciate the abundant contribution of genetic variation to the manifestation of atherosclerosis. Indeed, by now 164 chromosomal loci have been identified by genome-wide association studies (GWAS) to affect the risk of coronary artery disease...
August 2018: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/29973135/genome-wide-association-study-of-nocturnal-blood-pressure-dipping-in-hypertensive-patients
#9
Jenni M Rimpelä, Ilkka H Pörsti, Antti Jula, Terho Lehtimäki, Teemu J Niiranen, Lasse Oikarinen, Kimmo Porthan, Antti Tikkakoski, Juha Virolainen, Kimmo K Kontula, Timo P Hiltunen
BACKGROUND: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. METHODS: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo...
July 4, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29912321/genome-wide-studies-of-heart-failure-and-endophenotypes-lessons-learned-and-future-directions
#10
Maaike Yldau van der Ende, Mir Abdullah Said, Dirk Jan van Veldhuisen, Niek Verweij, Pim van der Harst
Heart failure (HF) is a complex clinical syndrome resulting from structural or functional impairments of ventricular filling or ejection of blood. HF has a poor prognosis and the burden to society remains tremendous. The unfulfilled expectation is that expanding our knowledge of the genetic architecture of HF will help to quickly advance the quality of risk assessment, diagnoses, and treatment. To date, genome-wide association studies (GWAS) of HF have led to disappointing results with only limited progress in our understanding and tempering the earlier expectations...
July 15, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29881931/recent-findings-in-the-genetics-of-blood-pressure-how-to-apply-in-practice-or-is-a-moonshot-required
#11
REVIEW
Sandosh Padmanabhan, Alisha Aman, Anna F Dominiczak
PURPOSE OF REVIEW: Hypertension is recognised as the biggest contributor to the global burden of disease, but it is controlled in less than a fifth of patients worldwide, despite being relatively easy to detect and the availability of inexpensive safe generic drugs. Blood pressure is regulated by a complex network of physiologic pathways with currently available drugs targeting key receptors or enzymes in the top pathways. Major advances in the dissection of both monogenic and polygenic determinants of blood pressure regulation and variation have not resulted in rapid translation of these discoveries into clinical applications or precision medicine...
June 7, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29849051/birth-weight-variants-are-associated-with-variable-fetal-intrauterine-growth-from-20-weeks-of-gestation
#12
L Engelbrechtsen, D Gybel-Brask, Y Mahendran, M Crusell, T H Hansen, T M Schnurr, E Hogdall, L Skibsted, T Hansen, H Vestergaard
Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8...
May 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29791233/association-of-a-chromosome-locus-9p21-3-cdkn2b-as1-variant-rs4977574-with-hypertension-the-tamrisk-study
#13
Tarja Kunnas, Jaakko Piesanen, Seppo T Nikkari
AIMS: Chromosome locus 9p21.3 CDKN2B antisense RNA 1 (CDKN2B-AS1) has been found to contain multiple genetic markers for coronary artery disease (CAD) by genome-wide association studies (GWAS). Of these, the association of variants rs4977574, rs10757274, and rs2383206 with hypertension was studied in the Tampere adult population cardiovascular risk study (TAMRISK). MATERIALS AND METHODS: A Finnish cohort of 336 subjects diagnosed with hypertension and 444 controls was analyzed...
May 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29666641/brief-overview-of-a-decade-of-genome-wide-association-studies-on-primary-hypertension
#14
REVIEW
Afifah Binti Azam, Elena Aisha Binti Azizan
Primary hypertension is widely believed to be a complex polygenic disorder with the manifestation influenced by the interactions of genomic and environmental factors making identification of susceptibility genes a major challenge. With major advancement in high-throughput genotyping technology, genome-wide association study (GWAS) has become a powerful tool for researchers studying genetically complex diseases. GWASs work through revealing links between DNA sequence variation and a disease or trait with biomedical importance...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29615742/systemic-and-specific-effects-of-antihypertensive-and-lipid-lowering-medication-on-plasma-protein-biomarkers-for-cardiovascular-diseases
#15
Stefan Enroth, Varun Maturi, Malin Berggrund, Sofia Bosdotter Enroth, Aristidis Moustakas, Åsa Johansson, Ulf Gyllensten
A large fraction of the adult population is on lifelong medication for cardiovascular disorders, but the metabolic consequences are largely unknown. This study determines the effects of common anti-hypertensive and lipid lowering drugs on circulating plasma protein biomarkers. We studied 425 proteins in plasma together with anthropometric and lifestyle variables, and the genetic profile in a cross-sectional cohort. We found 8406 covariate-protein associations, and a two-stage GWAS identified 17253 SNPs to be associated with 109 proteins...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29578190/uromodulin-rs4293393-t-c-variation-is-associated-with-kidney-disease-in-patients-with-type-2-diabetes
#16
Vinod Kumar, Ashok Kumar Yadav, Vivek Kumar, Anil Bhansali, Vivekanand Jha
Background & objectives: Uromodulin, a UMOD gene encoded glycoprotein is synthesized exclusively in renal tubular cells and released into urine. Mutations lead to uromodulin misfolding and retention in the kidney, where it might stimulate cells of immune system to cause inflammation and progression of kidney disease. Genome-wide association studies (GWAS) have identified UMOD locus to be associated with hypertension and diabetic nephropathy (DN). In this study, we investigated the association between rs4293393 variation in UMOD gene and susceptibility to kidney disease in individuals with type 2 diabetes mellitus (T2DM)...
November 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29531279/genome-wide-association-analysis-identifies-new-candidate-risk-loci-for-familial-intracranial-aneurysm-in-the-french-canadian-population
#17
Sirui Zhou, Ziv Gan-Or, Amirthagowri Ambalavanan, Dongbing Lai, Pingxing Xie, Cynthia V Bourassa, Stephanie Strong, Jay P Ross, Alexandre Dionne-Laporte, Dan Spiegelman, Nicolas Dupré, Tatiana M Foroud, Lan Xiong, Patrick A Dion, Guy A Rouleau
Intracranial Aneurysm (IA) is a common disease with a worldwide prevalence of 1-3%. In the French-Canadian (FC) population, where there is an important founder effect, the incidence of IA is higher and is frequently seen in families. In this study, we genotyped a cohort of 257 mostly familial FC IA patients and 1,992 FC controls using the Illumina NeuroX SNP-chip. The most strongly associated loci were tested in 34 Inuit IA families and in 32 FC IA patients and 106 FC controls that had been exome sequenced (WES)...
March 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29495593/advances-in-the-genetics-of-hypertension-the-effect-of-rare-variants
#18
REVIEW
Alessia Russo, Cornelia Di Gaetano, Giovanni Cugliari, Giuseppe Matullo
Worldwide, hypertension still represents a serious health burden with nine million people dying as a consequence of hypertension-related complications. Essential hypertension is a complex trait supported by multifactorial genetic inheritance together with environmental factors. The heritability of blood pressure (BP) is estimated to be 30-50%. A great effort was made to find genetic variants affecting BP levels through Genome-Wide Association Studies (GWAS). This approach relies on the "common disease-common variant" hypothesis and led to the identification of multiple genetic variants which explain, in aggregate, only 2-3% of the genetic variance of hypertension...
February 28, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29467655/atherosclerosis-is-an-inflammatory-disease-which-lacks-a-common-anti-inflammatory-therapy-how-human-genetics-can-help-to-this-issue-a-narrative-review
#19
REVIEW
Cristiano Fava, Martina Montagnana
Atherosclerosis is a multifactorial disease triggered and sustained by different risk factors such as dyslipidemia, arterial hypertension, diabetes mellitus, smoke, etc. Since a couple of decades, a pivotal role for inflammation in its pathogenesis has been recognized and proved at molecular levels, and already described in many animal models. Despite all this knowledge, due to the complexity of the specific inflammatory process subtending atherosclerosis and to the fact that inflammation is also a protective response against microorganisms, no anti-inflammatory therapy has been rendered available in the therapeutic armamentarium against atherosclerosis and vascular events till 2017 when canakinumab in the first ad-hoc randomized clinical trial (RCT) proved for the first time that targeting specifically inflammation lowers cardiovascular (CV) events...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29390587/prospective-association-of-a-genetic-risk-score-with-major-adverse-cardiovascular-events-in-patients-with-coronary-artery-disease
#20
Chen Zhao, Pin Zhu, Qile Shen, Li Jin
Many susceptibility loci associated with coronary artery disease (CAD) have been identified using genome-wide association studies (GWAS). This study aimed to examine whether a composite of single nucleotide polymorphisms (SNPs) derived from GWAS could identify the risk of major adverse cardiovascular events (MACEs) in patients with established CAD. There were 1059 patients with CAD were included in the analysis. Of the participants, 686 were on statin treatment at the start of follow-up. A weighted genetic risk score (wGRS) was calculated as the sum of risk alleles multiplied by the hazard ratio for a particular SNP...
December 2017: Medicine (Baltimore)
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