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https://www.readbyqxmd.com/read/29215398/a-genetic-risk-score-for-fasting-plasma-glucose-is-independently-associated-with-arterial-stiffness-a-mendelian-randomization-study
#1
Mikael Gottsäter, George Hindy, Marju Orho-Melander, Peter M Nilsson, Olle Melander
BACKGROUND: Arterial stiffness is known to be associated with a number of clinical conditions including hypertension, diabetes and dyslipidemia, and may predict cardiovascular events and mortality. However, causal links are hard to establish. Results from genome-wide association studies have identified only a few single nucleotide polymorphisms associated with arterial stiffness, the results have been inconsistent between studies and overlap with other clinical conditions is lacking. Our aim was to investigate a potential shared set of risk single nucleotide polymorphisms between relevant cardiometabolic traits and arterial stiffness...
December 5, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29198723/dna-methylation-analysis-identifies-loci-for-blood-pressure-regulation
#2
Melissa A Richard, Tianxiao Huan, Symen Ligthart, Rahul Gondalia, Min A Jhun, Jennifer A Brody, Marguerite R Irvin, Riccardo Marioni, Jincheng Shen, Pei-Chien Tsai, May E Montasser, Yucheng Jia, Catriona Syme, Elias L Salfati, Eric Boerwinkle, Weihua Guan, Thomas H Mosley, Jan Bressler, Alanna C Morrison, Chunyu Liu, Michael M Mendelson, André G Uitterlinden, Joyce B van Meurs, Oscar H Franco, Guosheng Zhang, Yun Li, James D Stewart, Joshua C Bis, Bruce M Psaty, Yii-Der Ida Chen, Sharon L R Kardia, Wei Zhao, Stephen T Turner, Devin Absher, Stella Aslibekyan, John M Starr, Allan F McRae, Lifang Hou, Allan C Just, Joel D Schwartz, Pantel S Vokonas, Cristina Menni, Tim D Spector, Alan Shuldiner, Coleen M Damcott, Jerome I Rotter, Walter Palmas, Yongmei Liu, Tomáš Paus, Steve Horvath, Jeffrey R O'Connell, Xiuqing Guo, Zdenka Pausova, Themistocles L Assimes, Nona Sotoodehnia, Jennifer A Smith, Donna K Arnett, Ian J Deary, Andrea A Baccarelli, Jordana T Bell, Eric Whitsel, Abbas Dehghan, Daniel Levy, Myriam Fornage
Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry...
November 30, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29194462/new-strategies-for-the-development-of-lipid-lowering-therapies-to-reduce-cardiovascular-risk
#3
Ian Graham, Chuck Shear, Pieter De Graeff, Caroline Boulton, Alberico L Catapano, Wendy Gattis Stough, Stefan C Carlsson, Guy De Backer, Joseph Emmerich, Scott Greenfeder, Albert M Kim, Dominik Lautsch, Tu Nguyen, Steven E Nissen, Krishna Prasad, Kausik Ray, Jennifer G Robinson, William J Sasiela, Karsten Bruins Slot, Erik Stroes, Tom Thuren, Bart Van der Schueren, Maja Velkovski-Rouyer, Scott M Wasserman, Olov Wiklund, Emmanouil Zouridakis
The very high occurrence of cardiovascular events presents a major public health issue because treatment remains suboptimal. Lowering low-density lipoprotein cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels. Opportunities for innovation in dyslipidaemia treatment should address the substantial risk of lipid-associated cardiovascular events among patients optimally treated per guidelines but who cannot achieve LDL-C goals, could benefit from additional LDL-C lowering therapy, or experience side effects of statins...
November 28, 2017: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/29188294/genetic-association-of-lipids-and-lipid-drug-targets-with-abdominal-aortic-aneurysm-a-meta-analysis
#4
Seamus C Harrison, Michael V Holmes, Stephen Burgess, Folkert W Asselbergs, Gregory T Jones, Annette F Baas, F N van 't Hof, Paul I W de Bakker, Jan D Blankensteijn, Janet T Powell, Athanasios Saratzis, Gert J de Borst, Daniel I Swerdlow, Yolanda van der Graaf, Andre M van Rij, David J Carey, James R Elmore, Gerard Tromp, Helena Kuivaniemi, Robert D Sayers, Nilesh J Samani, Matthew J Bown, Steve E Humphries
Importance: Risk factors for abdominal aortic aneurysm (AAA) are largely unknown, which has hampered the development of nonsurgical treatments to alter the natural history of disease. Objective: To investigate the association between lipid-associated single-nucleotide polymorphisms (SNPs) and AAA risk. Design, Setting, and Participants: Genetic risk scores, composed of lipid trait-associated SNPs, were constructed and tested for their association with AAA using conventional (inverse-variance weighted) mendelian randomization (MR) and data from international AAA genome-wide association studies...
November 29, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/29187356/dairy-consumption-and-body-mass-index-among-adults-mendelian-randomization-analysis-of-184802-individuals-from-25-studies
#5
(no author information available yet)
BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study...
November 29, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29187354/lactase-persistence-and-body-mass-index-the-contribution-of-mendelian-randomization
#6
EDITORIAL
Fernando Pires Hartwig, George Davey Smith
No abstract text is available yet for this article.
November 29, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29186515/assessment-of-moderate-coffee-consumption-and-risk-of-epithelial-ovarian-cancer-a-mendelian-randomization-study
#7
Jue-Sheng Ong, Liang-Dar Hwang, Gabriel Cuellar-Partida, Nicholas G Martin, Georgia Chenevix-Trench, Michael C J Quinn, Marilyn C Cornelis, Puya Gharahkhani, Penelope M Webb, Stuart MacGregor
Background: Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal. Methods: We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator...
November 25, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29178946/a-putative-causal-relationship-between-genetically-determined-female-body-shape-and-posttraumatic-stress-disorder
#8
Renato Polimanti, Ananda B Amstadter, Murray B Stein, Lynn M Almli, Dewleen G Baker, Laura J Bierut, Bekh Bradley, Lindsay A Farrer, Eric O Johnson, Anthony King, Henry R Kranzler, Adam X Maihofer, John P Rice, Andrea L Roberts, Nancy L Saccone, Hongyu Zhao, Israel Liberzon, Kerry J Ressler, Caroline M Nievergelt, Karestan C Koenen, Joel Gelernter
BACKGROUND: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. METHODS: We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls)...
November 27, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29174438/mendelian-randomization-analysis-of-cholesteryl-ester-transfer-protein-and-subclinical-atherosclerosis-a-population-based-study
#9
Tim Christen, Stella Trompet, Raymond Noordam, Lisanne L Blauw, Karin B Gast, Patrick C N Rensen, Ko Willems van Dijk, Frits R Rosendaal, Renée de Mutsert, J Wouter Jukema
BACKGROUND: Several trials to prevent cardiovascular disease by inhibiting cholesteryl ester transfer protein (CETP) have failed, except Randomized EValuation of the Effects of Anacetrapib through Lipid-modification. Thus far, it is unclear to what extent CETP is causally related to measures of atherosclerosis. OBJECTIVE: The aim of the article was to study the causal relationship between genetically determined CETP concentration and carotid intima-media thickness (cIMT) in a population-based cohort study...
November 2, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29171014/the-influence-of-big-clinical-data-and-genomics-on-precision-medicine-and-drug-development
#10
Joshua C Denny, Sara L Van Driest, Wei-Qi Wei, Dan M Roden
Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications...
November 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29169069/anti-inflammatory-agents-in-peripheral-arterial-disease
#11
REVIEW
Alexios S Antonopoulos, Evi Papanikolaou, Georgia Vogiatzi, Evangelos Oikonomou, Dimitris Tousoulis
Inflammation is pivotally involved in coronary and peripheral atherosclerotic disease. This established concept is based on both experimental animal models of vascular inflammation and Mendelian randomization studies demonstrating a causal relationship between pro-inflammatory cytokines (e.g. interleukin-6) and cardiovascular disease risk. More recently, the reduction of cardiovascular events by use of an interleukin-1β inhibitor (canakinumab) has revived interest in the use of anti-inflammatory agents for the treatment of atherosclerotic disease, including peripheral arterial disease...
November 20, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29165714/blood-lipid-genetic-scores-the-hmgcr-gene-and-cancer-risk-a-mendelian-randomization-study
#12
Marju Orho-Melander, George Hindy, Signe Borgquist, Christina-Alexandra Schulz, Jonas Manjer, Olle Melander, Tanja Stocks
Background: It is unclear whether there are causal associations between blood lipids, statin use and cancer risks. Under certain assumptions, Mendelian randomization analysis of a genetic marker for an exposure eliminates reverse causation and confounding. Methods: We applied Mendelian randomization analysis to genetic scores, comprising 26-41 single-nucleotide polymorphisms (SNPs), as instrumental variables (IVs) for triglycerides and low- and high-density lipoprotein cholesterol (LDLC, HDLC), using a prospective cohort of 26 904 individuals in which there were 6607 incident cancers...
November 20, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29164242/mendelian-randomization
#13
Connor A Emdin, Amit V Khera, Sekar Kathiresan
No abstract text is available yet for this article.
November 21, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29157668/iron-induced-rna-oxidation-in-the-general-population-and-in-mouse-tissue
#14
Vanja Cejvanovic, Laura Kofoed Kjær, Helle Kirstine Mørup Bergholdt, Arendse Torp-Pedersen, Trine Henriksen, Allan Weimann, Christina Ellervik, Henrik Enghusen Poulsen
Iron promotes formation of hydroxyl radicals by the Fenton reaction, subsequently leading to potential oxidatively generated damage of nucleic acids. Oxidatively generated damage to RNA, measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine, is increased in patients with genetic iron overload, which have led us to test the hypothesis that high iron status, assessed by iron biomarkers and genetic disposition, increases urinary excretion of 8-oxoGuo. In a general Danish population study we used a Mendelian randomization design with HFE genotypes as a proxy for iron status and supplemented with ex vivo experiments in mice muscle tissue exposed to iron(II) sulfate to attempt to clarify this hypothesis...
November 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29149250/modeling-the-causal-role-of-dna-methylation-in-the-association-between-cigarette-smoking-and-inflammation-in-african-americans-a-2-step-epigenetic-mendelian-randomization-study
#15
Min A Jhun, Jennifer A Smith, Erin B Ware, Sharon L R Kardia, Thomas H Mosley, Stephen T Turner, Patricia A Peyser, Sung Kyun Park
The association between cigarette smoking and inflammation is well known. However, the biological mechanisms behind the association are not fully understood, particularly the role of DNA methylation, which is known to be affected by smoking. Using 2-step epigenetic Mendelian randomization, we investigated the role of DNA methylation in the association between cigarette smoking and inflammation. In 822 African Americans from the Genetic Epidemiology Network of Arteriopathy, phase 2 (Jackson, Mississippi; 2000-2005), study population, we examined the association of cigarette smoking with DNA methylation using single nucleotide polymorphisms identified in previous genome-wide association studies of cigarette smoking...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29133521/circulating-total-bilirubin-and-future-risk-of-hypertension-in-the-general-population-the-prevention-of-renal-and-vascular-end-stage-disease-prevend-prospective-study-and-a-mendelian-randomization-approach
#16
Setor K Kunutsor, Lyanne M Kieneker, Stephen Burgess, Stephan J L Bakker, Robin P F Dullaart
BACKGROUND: Circulating total bilirubin is known to be inversely and independently associated with future risk of cardiovascular disease. However, the relationship of circulating total bilirubin with incident hypertension is uncertain. We aimed to assess the association of total bilirubin with future hypertension risk and supplemented this with a Mendelian randomization approach to investigate any causal relevance to the association. METHODS AND RESULTS: Plasma total bilirubin levels were measured at baseline in the PREVEND (Prevention of Renal and Vascular End-Stage Disease) prospective study of 3989 men and women without hypertension...
November 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29124703/vitamin-d-cardiovascular-disease-and-risk-factors
#17
Tea Skaaby, Betina H Thuesen, Allan Linneberg
Observational studies have suggested a possible protective role of vitamin D on the cardiovascular system. The available evidence does not support either cardiovascular benefits or harms of vitamin D supplementation. This chapter provides an overview and discussion of the current knowledge of vitamin D effects from a cardiovascular health perspective. It focuses on vitamin D in relation to cardiovascular disease, i.e. ischemic heart disease, and stroke; the traditional cardiovascular risk factors hypertension, abnormal blood lipids, obesity; and the emerging risk factors hyperparathyroidism, microalbuminuria, chronic obstructive pulmonary diseases, and non-alcoholic fatty liver disease...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29122815/evaluation-of-the-pleiotropic-effects-of-statins-a-reanalysis-of-the-randomized-trial-evidence-using-egger-regression
#18
Christopher Labos, James M Brophy, George Davey Smith, Allan D Sniderman, George Thanassoulis
OBJECTIVE: To reanalyze data from recent randomized trials of statins to assess whether the benefits and risks of statins are mediated primarily via their LDL-C (low-density lipoprotein cholesterol) lowering effects or via other mechanisms. APPROACH AND RESULTS: We adapted Egger regression, a technique frequently used in Mendelian randomization studies to detect genetic pleiotropy, to reanalyze the available randomized control trial data of statin therapy. For cardiovascular end points, each 1 mmol/L change in LDL-C with statin therapy was associated with a hazard ratio of 0...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29106476/correcting-the-standard-errors-of-2-stage-residual-inclusion-estimators-for-mendelian-randomization-studies
#19
Tom M Palmer, Michael V Holmes, Brendan J Keating, Nuala A Sheehan
Mendelian randomization studies use genotypes as instrumental variables to test for and estimate the causal effects of modifiable risk factors on outcomes. Two-stage residual inclusion (TSRI) estimators have been used when researchers are willing to make parametric assumptions. However, researchers are currently reporting uncorrected or heteroscedasticity-robust standard errors for these estimates. We compared several different forms of the standard error for linear and logistic TSRI estimates in simulations and in real-data examples...
November 1, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29106475/quantitative-serum-nuclear-magnetic-resonance-metabolomics-in-large-scale-epidemiology-a-primer-on-omic-technologies
#20
Peter Würtz, Antti J Kangas, Pasi Soininen, Debbie A Lawlor, George Davey Smith, Mika Ala-Korpela
Detailed metabolic profiling in large-scale epidemiologic studies has uncovered novel biomarkers for cardiometabolic diseases and clarified the molecular associations of established risk factors. A quantitative metabolomics platform based on nuclear magnetic resonance spectroscopy has found widespread use, already profiling over 400,000 blood samples. Over 200 metabolic measures are quantified per sample; in addition to many biomarkers routinely used in epidemiology, the method simultaneously provides fine-grained lipoprotein subclass profiling and quantification of circulating fatty acids, amino acids, gluconeogenesis-related metabolites, and many other molecules from multiple metabolic pathways...
November 1, 2017: American Journal of Epidemiology
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