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mendelian randomization

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https://www.readbyqxmd.com/read/28540979/alcohol-consumption-aldehyde-dehydrogenase-2-gene-polymorphisms-and-cardiovascular-health-in-korea
#1
REVIEW
Min Jeong Shin, Yoonsu Cho, George Davey Smith
Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations. A point mutation in the ALDH2 gene (the rs671 allele) yields an inactive form of ALDH2 that causes acetaldehyde accumulation in the body after alcohol consumption, thereby inhibiting normal alcohol metabolism...
July 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28534127/genetics-of-triglycerides-and-the-risk-of-atherosclerosis
#2
REVIEW
Jacqueline S Dron, Robert A Hegele
PURPOSE OF REVIEW: Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality...
July 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28533558/investigating-the-causal-effect-of-smoking-on-hay-fever-and-asthma-a-mendelian-randomization-meta-analysis-in-the-carta-consortium
#3
Tea Skaaby, Amy E Taylor, Rikke K Jacobsen, Lavinia Paternoster, Betina H Thuesen, Tarunveer S Ahluwalia, Sofus C Larsen, Ang Zhou, Andrew Wong, Maiken E Gabrielsen, Johan H Bjørngaard, Claudia Flexeder, Satu Männistö, Rebecca Hardy, Diana Kuh, Sarah J Barry, Line Tang Møllehave, Charlotte Cerqueira, Nele Friedrich, Tobias N Bonten, Raymond Noordam, Dennis O Mook-Kanamori, Christian Taube, Leon E Jessen, Alex McConnachie, Naveed Sattar, Mark N Upton, Charles McSharry, Klaus Bønnelykke, Hans Bisgaard, Holger Schulz, Konstantin Strauch, Thomas Meitinger, Annette Peters, Harald Grallert, Ellen A Nohr, Mika Kivimaki, Meena Kumari, Uwe Völker, Matthias Nauck, Henry Völzke, Chris Power, Elina Hyppönen, Torben Hansen, Torben Jørgensen, Oluf Pedersen, Veikko Salomaa, Niels Grarup, Arnulf Langhammer, Pål R Romundstad, Frank Skorpen, Jaakko Kaprio, Marcus R Munafò, Allan Linneberg
Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967)...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28528868/pleiotropic-effects-of-trait-associated-genetic-variation-on-dna-methylation-utility-for-refining-gwas-loci
#4
Eilis Hannon, Mike Weedon, Nicholas Bray, Michael O'Donovan, Jonathan Mill
Most genetic variants identified in genome-wide association studies (GWASs) of complex traits are thought to act by affecting gene regulation rather than directly altering the protein product. As a consequence, the actual genes involved in disease are not necessarily the most proximal to the associated variants. By integrating data from GWAS analyses with those from genetic studies of regulatory variation, it is possible to identify variants pleiotropically associated with both a complex trait and measures of gene regulation...
May 13, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28528403/assessing-the-causal-relationship-between-obesity-and-venous-thromboembolism-through-a-mendelian-randomization-study
#5
Sara Lindström, Marine Germain, Marta Crous-Bou, Erin N Smith, Pierre-Emmanuel Morange, Astrid van Hylckama Vlieg, Hugoline G de Haan, Daniel Chasman, Paul Ridker, Jennifer Brody, Mariza de Andrade, John A Heit, Weihong Tang, Immaculata DeVivo, Francine Grodstein, Nicholas L Smith, David Tregouet, Christopher Kabrhel
Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry...
May 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28527048/interpreting-findings-from-mendelian-randomization-using-the-mr-egger-method
#6
Stephen Burgess, Simon G Thompson
Mendelian randomization-Egger (MR-Egger) is an analysis method for Mendelian randomization using summarized genetic data. MR-Egger consists of three parts: (1) a test for directional pleiotropy, (2) a test for a causal effect, and (3) an estimate of the causal effect. While conventional analysis methods for Mendelian randomization assume that all genetic variants satisfy the instrumental variable assumptions, the MR-Egger method is able to assess whether genetic variants have pleiotropic effects on the outcome that differ on average from zero (directional pleiotropy), as well as to provide a consistent estimate of the causal effect, under a weaker assumption-the InSIDE (INstrument Strength Independent of Direct Effect) assumption...
May 19, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28515069/mendelian-randomization-shows-sex-specific-associations-between-long-chain-pufa-related-genotypes-and-cognitive-performance-in-danish-schoolchildren
#7
Lotte Lauritzen, Louise B Sørensen, Laurine B Harsløf, Christian Ritz, Ken D Stark, Arne Astrup, Camilla B Dyssegaard, Niels Egelund, Kim F Michaelsen, Camilla T Damsgaard
Background: Dietary and endogenously formed long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to improve cognitive development, but results are inconclusive, with suggestions of sex specificity. One study suggested that single-nucleotide polymorphisms (SNPs) rs1535 and rs174448 in the fatty acid desaturase (FADS) gene cluster have opposite effects on erythrocyte LCPUFAs at 9 mo.Objective: To explore whether SNPs in FADS and elongase (ELOVL) genes were associated with school performance in a sex-specific manner, we performed a Mendelian randomization study using data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study with 765 Danish schoolchildren 8-11 y old...
May 17, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28515044/exploring-the-causal-pathway-from-telomere-length-to-coronary-heart-disease-a-network-mendelian-randomization-study
#8
Yiqiang Zhan, Ida K Karlsson, Robert Karlsson, Annika Tillander, Chandra A Reynolds, Nancy L Pedersen, Sara Hägg
Rationale: Observational studies have found shorter leukocyte telomere length to be a risk factor for coronary heart disease (CHD), and more recently the association was suggested to be causal. However, the relationship between telomere length and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from telomere length to CHD warrants further attention. Objective: To examine if metabolic risk factors for CHD mediate the causal pathway from short telomere length to increased risk of CHD using a network Mendelian randomization (MR) design...
May 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28504983/serum-inhibitory-factor-1-high-density-lipoprotein-and-cardiovascular-diseases
#9
Laurent O Martinez, Annelise Genoux, Jean Ferrières, Thibaut Duparc, Bertrand Perret
PURPOSE OF REVIEW: The atheroprotective properties of HDL are supported by epidemiological and preclinical research. However, the results of interventional trials paradoxically indicate that drugs increasing HDL-cholesterol (HDL-C) do not reduce coronary artery disease (CAD) risk. Moreover, Mendelian randomization studies have shown no effect of HDL-C-modifying variants on CAD outcome. Thus, the protective effects of HDL particles are more governed by their functional status than their cholesterol content...
May 12, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28500271/causal-associations-of-adiposity-and-body-fat-distribution-with-coronary-heart-disease-stroke-subtypes-and-type-2-diabetes-a-mendelian-randomization-analysis
#10
Caroline Dale, Ghazaleh Fatemifar, Tom Palmer, Jonathan White, David Prieto-Merino, Delilah Zabaneh, Jorgen E L Engmann, Tina Shah, Andrew Wong, Helen R Warren, Stela McLachlan, Stella Trompet, Max Moldovan, Richard W Morris, Reecha Sofat, Meena Kumari, Elina Hyppönen, Barbara J Jefferis, Tom R Gaunt, Yoav Ben-Shlomo, Ang Zhou, Aleksandra Gentry-Maharaj, Andy Ryan, Renée de Mutsert, Raymond Noordam, Mark J Caulfield, J Wouter Jukema, Bradford B Worrall, Patricia B Munroe, Usha Menon, Chris Power, Diana Kuh, Debbie A Lawlor, Steve E Humphries, Dennis O Mook-Kanamori, George Davey Smith, Naveed Sattar, Mika Kivimaki, Jacqueline F Price, Frank Dudbridge, Aroon D Hingorani, Michael V Holmes, Juan-Pablo Casas
Background -Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. Methods -97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia...
May 12, 2017: Circulation
https://www.readbyqxmd.com/read/28493302/instrumental-variables-estimation-of-exposure-effects-on-a-time-to-event-endpoint-using-structural-cumulative-survival-models
#11
Torben Martinussen, Stijn Vansteelandt, Eric J Tchetgen Tchetgen, David M Zucker
The use of instrumental variables for estimating the effect of an exposure on an outcome is popular in econometrics, and increasingly so in epidemiology. This increasing popularity may be attributed to the natural occurrence of instrumental variables in observational studies that incorporate elements of randomization, either by design or by nature (e.g., random inheritance of genes). Instrumental variables estimation of exposure effects is well established for continuous outcomes and to some extent for binary outcomes...
May 10, 2017: Biometrics
https://www.readbyqxmd.com/read/28490510/nonfermented-milk-and-other-dairy-products-associations-with-all-cause-mortality
#12
Gianluca Tognon, Lena M Nilsson, Dmitry Shungin, Lauren Lissner, Jan-Håkan Jansson, Frida Renström, Maria Wennberg, Anna Winkvist, Ingegerd Johansson
Background: A positive association between nonfermented milk intake and increased all-cause mortality was recently reported, but overall, the association between dairy intake and mortality is inconclusive.Objective: We studied associations between intake of dairy products and all-cause mortality with an emphasis on nonfermented milk and fat content.Design: A total of 103,256 adult participants (women: 51.0%) from Northern Sweden were included (7121 deaths; mean follow-up: 13.7 y). Associations between all-cause mortality and reported intakes of nonfermented milk (total or by fat content), fermented milk, cheese, and butter were tested with the use of Cox proportional hazards models that were adjusted for age, sex, body mass index, smoking status, education, energy intake, examination year, and physical activity...
May 10, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28486474/vitamin-d-levels-and-susceptibility-to-asthma-elevated-immunoglobulin-e-levels-and-atopic-dermatitis-a-mendelian-randomization-study
#13
Despoina Manousaki, Lavinia Paternoster, Marie Standl, Miriam F Moffatt, Martin Farrall, Emmanuelle Bouzigon, David P Strachan, Florence Demenais, Mark Lathrop, William O C M Cookson, J Brent Richards
BACKGROUND: Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. METHODS AND FINDINGS: We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation...
May 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28483601/rcts-are-the-only-appropriate-way-to-demonstrate-the-role-of-vitamin-d-in-health
#14
REVIEW
Rolf Jorde
Despite thousands of vitamin D studies published, including hundreds of reviews and meta-analyses, it is still uncertain if supplementation with vitamin D will have positive health effects, except for the skeleton. This cannot be answered by doing more observational studies as it is impossible to control for confounding factors and reverse causality. The only way to firmly prove positive vitamin D effects is by doing the properly designed randomized controlled trials (RCTs). However, it has been difficult to show the expected positive effects by vitamin D supplementation in RCTs, which may indicate that the effects, if present must be small...
May 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28477314/the-role-of-emerging-risk-factors-in-cardiovascular-outcomes
#15
REVIEW
Ben Lacey, William G Herrington, David Preiss, Sarah Lewington, Jane Armitage
PURPOSE OF REVIEW: This review discusses the recent evidence for a selection of blood-based emerging risk factors, with particular reference to their relation with coronary heart disease and stroke. RECENT FINDINGS: For lipid-related emerging risk factors, recent findings indicate that increasing high-density lipoprotein cholesterol is unlikely to reduce cardiovascular risk, whereas reducing triglyceride-rich lipoproteins and lipoprotein(a) may be beneficial. For inflammatory and hemostatic biomarkers, genetic studies suggest that IL-6 (a pro-inflammatory cytokine) and several coagulation factors are causal for cardiovascular disease, but such studies do not support a causal role for C-reactive protein and fibrinogen...
June 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28472508/mendelian-randomization-for-investigating-causal-roles-of-biomarkers-in-multifactorial-health-outcomes-a-lesson-from-studies-on-liver-biomarkers
#16
Ali Abbasi
No abstract text is available yet for this article.
May 2, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28472354/lessons-from-mendelian-randomization-studies-on-liver-biomarkers-response-to-letter-by-a-abbasi
#17
Raymond Noordam, Roelof A J Smit, Iris Postmus, Stella Trompet, Diana van Heemst
No abstract text is available yet for this article.
May 2, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28468080/-mendelian-randomization-approach-used-for-causal-inferences
#18
L N Wang, Zuofeng Zhang
Mendelian randomization (MR) approach is based on the Mendelian genetic law, which is called "Parental alleles that randomly assigned to the offspring" . MR refers to the use of genetic variants to develop causal inferences from observational data, if the variant genotype is associated with the phenotype and the variant genotype associated with the risk of disease of interest through the phenotype. Hence, the genotype can be used as Instrumental Variable (IV) to infer the causal relation between the phenotype and the risk of diseases...
April 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28456421/mendelian-randomization-implicates-high-density-lipoprotein-cholesterol-associated-mechanisms-in-etiology-of-age-related-macular-degeneration
#19
Stephen Burgess, George Davey Smith
PURPOSE: Undertake a systematic investigation into associations between genetic predictors of lipid fractions and age-related macular degeneration (AMD) risk. DESIGN: Two-sample Mendelian randomization investigation using published data. PARTICIPANTS: A total of 33 526 individuals (16 144 cases, 17 832 controls) predominantly of European ancestry from the International Age-related Macular Degeneration Genomics Consortium. METHODS: We consider 185 variants previously demonstrated to be associated with at least 1 of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides at a genome-wide level of significance, and test their associations with AMD...
April 26, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28453778/exploring-a-causal-role-of-dna-methylation-in-the-relationship-between-maternal-vitamin-b12-during-pregnancy-and-child-s-iq-at-age-8-cognitive-performance-and-educational-attainment-a-two-step-mendelian-randomization-study
#20
Doretta Caramaschi, Gemma C Sharp, Ellen A Nohr, Katie Berryman, Sarah J Lewis, George Davey Smith, Caroline L Relton
An adequate intake of vitamin B12 during pregnancy plays an important role in offspring neurodevelopment, potentially via epigenetic processes. We used a two-step Mendelian randomization approach to assess whether DNA methylation plays a mediating and causal role in associations between maternal vitamin B12 status and offspring's cognition. Firstly, we estimated the causal effect of maternal vitamin B12 levels on cord blood DNA methylation using the maternal FUT2 genotypes rs492602:A>G and rs1047781:A>T as proxies for circulating vitamin B12 levels in the Avon Longitudinal Study of Parents and Children (ALSPAC) and we tested the observed associations in a replication cohort...
April 27, 2017: Human Molecular Genetics
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