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https://www.readbyqxmd.com/read/27909909/obesity-biomarkers-metabolism-and-risk-of-cancer-an-epidemiological-perspective
#1
Katharina Nimptsch, Tobias Pischon
Obesity is associated with metabolic alterations that may pose a biological link between body fatness and risk of cancer. Elucidating the role of obesity-related biomarkers in cancer development is essential for developing targeted strategies aiming at obesity-associated cancer prevention. Molecular epidemiological studies of the past decades have provided evidence that major hormonal pathways linking obesity and cancer risk include the insulin and insulin-like growth factor-1 (IGF-1) axis, sex-steroid hormones, adipokines and chronic low-grade inflammation...
2016: Recent Results in Cancer Research
https://www.readbyqxmd.com/read/27903934/large-differences-in-adiponectin-levels-have-no-clear-effect-on-multiple-sclerosis-risk-a-mendelian-randomization-study
#2
Julia Devorak, Lauren E Mokry, John A Morris, Vincenzo Forgetta, George Davey Smith, Stephen Sawcer, J Brent Richards
BACKGROUND: Mendelian randomization (MR) studies have demonstrated strong support for an association between genetically increased body mass index and risk of multiple sclerosis (MS). The adipokine adiponectin may be a potential mechanism linking body mass to risk of MS. OBJECTIVE: To evaluate whether genetically increased adiponectin levels influence risk of MS. METHODS: Using genome-wide significant single nucleotide polymorphisms (SNPs) for adiponectin, we undertook an MR study to estimate the effect of adiponectin on MS...
November 30, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27901035/homocysteine-reducing-b-vitamins-and-ischemic-heart-disease-a-separate-sample-mendelian-randomization-analysis
#3
J V Zhao, C M Schooling
BACKGROUND/OBJECTIVES: Observationally, homocysteine is positively associated with ischemic heart disease (IHD) and unhealthy lipids; folate and vitamin B12, which reduce homocysteine, are associated with lower IHD risk and healthy lipids. Randomized controlled trials have shown no benefits of folate and vitamin B12 for IHD. To clarify the role of these potential targets of intervention in IHD we assessed how genetically determined homocysteine, folate and vitamin-B12-affected IHD and lipids...
November 30, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27892412/commentary-mendelian-randomization-analysis-identifies-circulating-vitamin-d-as-a-causal-risk-factor-for-ovarian-cancer
#4
Caroline J Bull, James Yarmolinsky, Kaitlin H Wade
No abstract text is available yet for this article.
October 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/27868358/resolving-microsatellite-genotype-ambiguity-in-populations-of-allopolyploid-and-diploidized-autopolyploid-organisms-using-negative-correlations-between-allelic-variables
#5
Lindsay V Clark, Andrea Drauch Schreier
A major limitation in the analysis of genetic marker data from polyploid organisms is non-Mendelian segregation, particularly when a single marker yields allelic signals from multiple, independently segregating loci (isoloci). However, with markers such as microsatellites that detect more than two alleles, it is sometimes possible to deduce which alleles belong to which isoloci. Here we describe a novel mathematical property of codominant marker data when it is recoded as binary (presence/absence) allelic variables: under random mating in an infinite population, two allelic variables will be negatively correlated if they belong to the same locus, but uncorrelated if they belong to different loci...
November 21, 2016: Molecular Ecology Resources
https://www.readbyqxmd.com/read/27863359/is-hyperhomocysteinemia-a-causal-factor-for-heart-failure-the-impact-of-the-functional-variants-of-mthfr-and-pon1-on-ischemic-and-non-ischemic-etiology
#6
Ewa Strauss, Wieslaw Supinski, Artur Radziemski, Grzegorz Oszkinis, Andrzej Leon Pawlak, Jerzy Gluszek
BACKGROUND: Hyperhomocysteinemia was found to be uniformly associated with the development of heart failure (HF) and HF mortality; however, it is uncertain whether this relation is causative or not. We used Mendelian randomization to examine the associations of the methylene tetrahydrofolate gene (MTHFR) and paraoxonase 1 gene (PON1) variants as a proxy for lifelong exposure to high Hcy and Hcy-thiolactone concentrations with the development of HF in men aged ≤60years and the occurrence of adverse effects at one-year follow-up...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27863252/the-allelic-landscape-of-human-blood-cell-trait-variation-and-links-to-common-complex-disease
#7
William J Astle, Heather Elding, Tao Jiang, Dave Allen, Dace Ruklisa, Alice L Mann, Daniel Mead, Heleen Bouman, Fernando Riveros-Mckay, Myrto A Kostadima, John J Lambourne, Suthesh Sivapalaratnam, Kate Downes, Kousik Kundu, Lorenzo Bomba, Kim Berentsen, John R Bradley, Louise C Daugherty, Olivier Delaneau, Kathleen Freson, Stephen F Garner, Luigi Grassi, Jose Guerrero, Matthias Haimel, Eva M Janssen-Megens, Anita Kaan, Mihir Kamat, Bowon Kim, Amit Mandoli, Jonathan Marchini, Joost H A Martens, Stuart Meacham, Karyn Megy, Jared O'Connell, Romina Petersen, Nilofar Sharifi, Simon M Sheard, James R Staley, Salih Tuna, Martijn van der Ent, Klaudia Walter, Shuang-Yin Wang, Eleanor Wheeler, Steven P Wilder, Valentina Iotchkova, Carmel Moore, Jennifer Sambrook, Hendrik G Stunnenberg, Emanuele Di Angelantonio, Stephen Kaptoge, Taco W Kuijpers, Enrique Carrillo-de-Santa-Pau, David Juan, Daniel Rico, Alfonso Valencia, Lu Chen, Bing Ge, Louella Vasquez, Tony Kwan, Diego Garrido-Martín, Stephen Watt, Ying Yang, Roderic Guigo, Stephan Beck, Dirk S Paul, Tomi Pastinen, David Bujold, Guillaume Bourque, Mattia Frontini, John Danesh, David J Roberts, Willem H Ouwehand, Adam S Butterworth, Nicole Soranzo
Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27856775/genetically-decreased-vitamin-d-and-risk-of-alzheimer-disease
#8
Lauren E Mokry, Stephanie Ross, John A Morris, Despoina Manousaki, Vincenzo Forgetta, J Brent Richards
OBJECTIVE: To test whether genetically decreased vitamin D levels are associated with Alzheimer disease (AD) using mendelian randomization (MR), a method that minimizes bias due to confounding or reverse causation. METHODS: We selected single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels (p < 5 × 10(-8)) from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) Consortium (N = 33,996) to act as instrumental variables for the MR study...
November 16, 2016: Neurology
https://www.readbyqxmd.com/read/27846416/stature-and-long-term-labor-market-outcomes-evidence-using-mendelian-randomization
#9
Petri Böckerman, Jutta Viinikainen, Jari Vainiomäki, Mirka Hintsanen, Niina Pitkänen, Terho Lehtimäki, Jaakko Pehkonen, Suvi Rovio, Olli Raitakari
We use the Young Finns Study (N=∼2000) on the measured height linked to register-based long-term labor market outcomes. The data contain six age cohorts (ages 3, 6, 9, 12, 15 and 18, in 1980) with the average age of 31.7, in 2001, and with the female share of 54.7. We find that taller people earn higher earnings according to the ordinary least squares (OLS) estimation. The OLS models show that 10cm of extra height is associated with 13% higher earnings. We use Mendelian randomization, with the genetic score as an instrumental variable (IV) for height to account for potential confounders that are related to socioeconomic background, early life conditions and parental investments, which are otherwise very difficult to fully account for when using covariates in observational studies...
November 8, 2016: Economics and Human Biology
https://www.readbyqxmd.com/read/27845333/habitual-coffee-consumption-and-risk-of-type-2-diabetes-ischemic-heart-disease-depression-and-alzheimer-s-disease-a-mendelian-randomization-study
#10
Man Ki Kwok, Gabriel M Leung, C Mary Schooling
Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer's disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer's disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27835897/enhanced-circulating-transforming-growth-factor-beta-1-is-causally-associated-with-an-increased-risk-of-hepatocellular-carcinoma-a-mendelian-randomization-meta-analysis
#11
Wei-Qun Lu, Ji-Liang Qiu, Zhi-Liang Huang, Hai-Ying Liu
The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815829/genetics-current-and-future-role-in-the-prevention-and-management-of-coronary-artery-disease
#12
REVIEW
Robert Roberts
PURPOSE OF REVIEW: The purpose of this study is to review genetic risk variants for coronary artery disease (CAD) and how they will change the management and prevention of CAD currently and in the future. RECENT FINDINGS: Through the efforts of international consortia, 58 genetic risk variants for CAD of genome-wide significance have been replicated in appropriate independent populations. Only one third of these variants mediate their risk through known conventional risk factors for CAD...
December 2016: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/27813215/mendelian-randomization-analysis-of-a-time-varying-exposure-for-binary-disease-outcomes-using-functional-data-analysis-methods
#13
Ying Cao, Suja S Rajan, Peng Wei
A Mendelian randomization (MR) analysis is performed to analyze the causal effect of an exposure variable on a disease outcome in observational studies, by using genetic variants that affect the disease outcome only through the exposure variable. This method has recently gained popularity among epidemiologists given the success of genetic association studies. Many exposure variables of interest in epidemiological studies are time varying, for example, body mass index (BMI). Although longitudinal data have been collected in many cohort studies, current MR studies only use one measurement of a time-varying exposure variable, which cannot adequately capture the long-term time-varying information...
December 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/27808046/-obesity-increases-the-risk-of-cardiovascular-disease
#14
Shoaib Afzal, Børge Grønne Nordestgaard
Evidence from epidemiology, randomized intervention trials, and Mendelian randomization studies indicates that obesity is causally associated with increased burden of cardiovascular disease risk factors and increased risk of cardiovascular disease. This association is probably mediated by modifiable risk factors; thus indicating that primary prevention with weight loss and treatment of obesity-related risk factors for cardiovascular disease will reduce cardiovascular disease in the general population.
October 31, 2016: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/27768686/effect-of-insulin-resistance-on-monounsaturated-fatty-acid-levels-a-multi-cohort-non-targeted-metabolomics-and-mendelian-randomization-study
#15
Christoph Nowak, Samira Salihovic, Andrea Ganna, Stefan Brandmaier, Taru Tukiainen, Corey D Broeckling, Patrik K Magnusson, Jessica E Prenni, Rui Wang-Sattler, Annette Peters, Konstantin Strauch, Thomas Meitinger, Vilmantas Giedraitis, Johan Ärnlöv, Christian Berne, Christian Gieger, Samuli Ripatti, Lars Lind, Nancy L Pedersen, Johan Sundström, Erik Ingelsson, Tove Fall
Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27749700/sensitivity-analyses-for-robust-causal-inference-from-mendelian-randomization-analyses-with-multiple-genetic-variants
#16
Stephen Burgess, Jack Bowden, Tove Fall, Erik Ingelsson, Simon G Thompson
Mendelian randomization investigations are becoming more powerful and simpler to perform, due to the increasing size and coverage of genome-wide association studies and the increasing availability of summarized data on genetic associations with risk factors and disease outcomes. However, when using multiple genetic variants from different gene regions in a Mendelian randomization analysis, it is highly implausible that all the genetic variants satisfy the instrumental variable assumptions. This means that a simple instrumental variable analysis alone should not be relied on to give a causal conclusion...
January 2017: Epidemiology
https://www.readbyqxmd.com/read/27741566/investigating-the-possible-causal-role-of-coffee-consumption-with-prostate-cancer-risk-and-progression-using-mendelian-randomization-analysis
#17
Amy E Taylor, Richard M Martin, Milan S Geybels, Janet L Stanford, Irene Shui, Rosalind Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A Haiman, Johanna Schleutker, Børge G Nordestgaard, Ruth C Travis, David Neal, Nora Pashayan, Kay-Tee Khaw, William Blot, Stephen Thibodeau, Christiane Maier, Adam S Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Park, Radka Kaneva, Jyotsna Batra, Manuel R Teixeira, Hardev Pandha, Jenny Donovan, Marcus R Munafò
Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium...
January 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27702834/systolic-blood-pressure-and-risk-of-type-2-diabetes-a-mendelian-randomization-study
#18
Rachael C Aikens, Wei Zhao, Danish Saleheen, Muredach P Reilly, Stephen E Epstein, Emmi Tikkanen, Veikko Salomaa, Benjamin F Voight
Observational studies have shown that elevated systolic blood pressure (SBP) is associated with future onset of type 2 diabetes, but whether this association is causal is not known. We applied the Mendelian Randomization framework to evaluate the causal hypothesis that elevated SBP increases risk to type 2 diabetes. We utilized 28 genetic variants associated with SBP and evaluated their impact on type 2 diabetes using a European-centric meta-analysis comprising 37,293 cases and 125,686 controls. We found that elevation of SBP levels by 1 mmHg due to our genetic score was associated with a 2% increase in risk of type 2 diabetes (OR=1...
October 4, 2016: Diabetes
https://www.readbyqxmd.com/read/27687604/is-high-density-lipoprotein-cholesterol-causally-related-to-kidney-function-evidence-from-genetic-epidemiological-studies
#19
Stefan Coassin, Salome Friedel, Anna Köttgen, Claudia Lamina, Florian Kronenberg
OBJECTIVE: A recent observational study with almost 2 million men reported an association between low high-density lipoprotein (HDL) cholesterol and worse kidney function. The causality of this association would be strongly supported if genetic variants associated with HDL cholesterol were also associated with kidney function. APPROACH AND RESULTS: We used 68 genetic variants (single-nucleotide polymorphisms [SNPs]) associated with HDL cholesterol in genome-wide association studies including >188 000 subjects and tested their association with estimated glomerular filtration rate (eGFR) using summary statistics from another genome-wide association studies of kidney function including ≤133 413 subjects...
September 29, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27677946/lipoprotein-a-as-a-cause-of-cardiovascular-disease-insights-from-epidemiology-genetics-and-biology
#20
REVIEW
Børge G Nordestgaard, Anne Langsted
Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly supports that elevated lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve stenosis. The Mendelian randomization approach used to infer causality is generally not affected by confounding and reverse causation, the major problems of observational epidemiology. This approach is particularly valuable to study causality of Lp(a), as single genetic variants exist that explain 27-28% of all variation in plasma Lp(a)...
November 2016: Journal of Lipid Research
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