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GWAS and hypertension

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https://www.readbyqxmd.com/read/30110940/pervasive-modulation-of-obesity-risk-by-the-environment-and-genomic-background
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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)
https://www.readbyqxmd.com/read/29329304/a-novel-method-to-test-associations-between-a-weighted-combination-of-phenotypes-and-genetic-variants
#15
Huanhuan Zhu, Shuanglin Zhang, Qiuying Sha
Many complex diseases like diabetes, hypertension, metabolic syndrome, et cetera, are measured by multiple correlated phenotypes. However, most genome-wide association studies (GWAS) focus on one phenotype of interest or study multiple phenotypes separately for identifying genetic variants associated with complex diseases. Analyzing one phenotype or the related phenotypes separately may lose power due to ignoring the information obtained by combining phenotypes, such as the correlation between phenotypes. In order to increase statistical power to detect genetic variants associated with complex diseases, we develop a novel method to test a weighted combination of multiple phenotypes (WCmulP)...
2018: PloS One
https://www.readbyqxmd.com/read/29272997/genome-variation-and-conserved-regulation-identify-genomic-regions-responsible-for-strain-specific-phenotypes-in-rat
#16
David Martín-Gálvez, Denis Dunoyer de Segonzac, Man Chun John Ma, Anne E Kwitek, David Thybert, Paul Flicek
BACKGROUND: The genomes of laboratory rat strains are characterised by a mosaic haplotype structure caused by their unique breeding history. These mosaic haplotypes have been recently mapped by extensive sequencing of key strains. Comparison of genomic variation between two closely related rat strains with different phenotypes has been proposed as an effective strategy for the discovery of candidate strain-specific regions involved in phenotypic differences. We developed a method to prioritise strain-specific haplotypes by integrating genomic variation and genomic regulatory data predicted to be involved in specific phenotypes...
December 22, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29176593/shared-genetic-etiology-of-hypertension-and-stroke-evidence-from-bioinformatics-analysis-of-genome-wide-association-studies
#17
L D Ji, S P Hu, J Y Li, B B Yao, Q J Shen, J Xu
Hypertension is the most significant modifiable risk factor for cerebrovascular disease. It has been estimated that about 54% of strokes worldwide can be attributed to hypertension. However, there has not been a systematic study assessing the shared genetic susceptibility to hypertension and stroke on a genome-wide level. In this study, SNPs associated with essential hypertension and stroke were collected from the NHGRI-EBI GWAS catalog, and genotype imputation were conducted using information from the 1000 Genomes Project...
December 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/29138037/genetic-predisposition-to-preeclampsia-is-conferred-by-fetal-dna-variants-near-flt1-a-gene-involved-in-the-regulation-of-angiogenesis
#18
REVIEW
Kathryn J Gray, Richa Saxena, S Ananth Karumanchi
Preeclampsia risk is influenced by both the mother's genetic background and the genetics of her fetus; however, the specific genes responsible for conferring preeclampsia risk have largely remained elusive. Evidence that preeclampsia has a genetic predisposition was first detailed in the early 1960s, and overall preeclampsia heritability is estimated at ∼55%. Many traditional gene discovery approaches have been used to investigate the specific genes that contribute to preeclampsia risk, but these have largely not been successful or reproducible...
February 2018: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29113935/predicting-age-by-mining-electronic-medical-records-with-deep-learning-characterizes-differences-between-chronological-and-physiological-age
#19
Zichen Wang, Li Li, Benjamin S Glicksberg, Ariel Israel, Joel T Dudley, Avi Ma'ayan
Determining the discrepancy between chronological and physiological age of patients is central to preventative and personalized care. Electronic medical records (EMR) provide rich information about the patient physiological state, but it is unclear whether such information can be predictive of chronological age. Here we present a deep learning model that uses vital signs and lab tests contained within the EMR of Mount Sinai Health System (MSHS) to predict chronological age. The model is trained on 377,686 EMR from patients of ages 18-85 years old...
December 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/29045471/parental-and-offspring-contribution-of-genetic-markers-of-adult-blood-pressure-in-early-life-the-family-study
#20
Sébastien Robiou-du-Pont, Sonia S Anand, Katherine M Morrison, Sarah D McDonald, Stephanie A Atkinson, Koon K Teo, David Meyre
Previous genome wide association studies (GWAS) identified associations of multiple common variants with diastolic and systolic blood pressure traits in adults. However, the contribution of these loci to variations of blood pressure in early life is unclear. We assessed the child and parental contributions of 33 GWAS single-nucleotide polymorphisms (SNPs) for blood pressure in 1,525 participants (515 children, 406 mothers and 237 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) study followed-up for 5 years...
2017: PloS One
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