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mendelian randomization

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https://www.readbyqxmd.com/read/28922377/c-reactive-protein-upregulates-the-whole-blood-expression-of-cd59-an-integrative-analysis
#1
Kaido Lepik, Tarmo Annilo, Viktorija Kukuškina, Kai Kisand, Zoltán Kutalik, Pärt Peterson, Hedi Peterson
Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes...
September 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28921927/fast-and-cost-effective-single-nucleotide-polymorphism-snp-detection-in-the-absence-of-a-reference-genome-using-semi-deep-next-generation-random-amplicon-sequencing-ramseq
#2
Helmut Bayerl, Robert H S Kraus, Carsten Nowak, Daniel W Foerster, Joerns Fickel, Ralph Kuehn
Biodiversity has suffered a dramatic global decline during the past decades and monitoring tools are urgently needed providing data for the development and evaluation of conservation efforts both on a species and a genetic level. However, in wild species the assessment of genetic diversity is often hampered by the lack of suitable genetic markers. In this article we present Random Amplicon Sequencing (RAMseq), a novel approach for fast and cost-effective detection of single nucleotide polymorphisms (SNPs) in non-model species by semi-deep sequencing of random amplicons...
September 15, 2017: Molecular Ecology Resources
https://www.readbyqxmd.com/read/28910285/correction-effect-of-insulin-resistance-on-monounsaturated-fatty-acid-levels-a-multi-cohort-non-targeted-metabolomics-and-mendelian-randomization-study
#3
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
[This corrects the article DOI: 10.1371/journal.pgen.1006379.].
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28891071/genetic-variation-in-the-vitamin-d-related-pathway-and-breast-cancer-risk-in-women-of-african-ancestry-in-the-root-consortium
#4
Shengfeng Wang, Dezheng Huo, Sonia Kupfer, Dereck Alleyne, Temidayo O Ogundiran, Oladosu Ojengbede, Wei Zheng, Katherine L Nathanson, Barbara Nemesure, Stefan Ambs, Olufunmilayo I Olopade, Yonglan Zheng
The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single-nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome-wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP-level...
September 10, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28877919/high-lipoprotein-a-and-low-risk-of-major-bleeding-in-brain-and-airways-in-the-general-population-a-mendelian-randomization-study
#5
Anne Langsted, Pia R Kamstrup, Børge G Nordestgaard
BACKGROUND: The physiological role of lipoprotein(a) is unclear; however, lipoprotein(a) may play a role in hemostasis and wound healing. We tested the hypothesis that high lipoprotein(a) concentrations are associated with low risk of major bleeding in the brain and airways both observationally and causally (from human genetics). METHODS: We examined 109169 individuals from the Copenhagen City Heart Study and the Copenhagen General Population study, 2 similar prospective studies conducted in the Danish general population...
September 6, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28876462/the-causal-role-of-alcohol-use-in-adolescent-externalizing-and-internalizing-problems-a-mendelian-randomization-study
#6
Miao Chao, Xinying Li, Matt McGue
BACKGROUND: The co-occurrence of alcohol use and externalizing/internalizing problems threatens adolescents' mental health. Research on whether alcohol use and these problems are causal and the direction of the potential causal relationships is needed to understand the mechanisms of the co-occurrence. METHOD: A Mendelian randomization analysis was conducted in which the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol use phenotypes...
September 6, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28866807/association-between-lipoprotein-a-level-and-type-2-diabetes-no-evidence-for-a-causal-role-of-lipoprotein-a-and-insulin
#7
Nikolaus Buchmann, Markus Scholz, Christina M Lill, Ralph Burkhardt, Rahel Eckardt, Kristina Norman, Markus Loeffler, Lars Bertram, Joachim Thiery, Elisabeth Steinhagen-Thiessen, Ilja Demuth
AIMS: Inverse relationships have been described between the largely genetically determined levels of serum/plasma lipoprotein(a) [Lp(a)], type 2 diabetes (T2D) and fasting insulin. Here, we aimed to evaluate the nature of these relationships with respect to causality. METHODS: We tested whether we could replicate the recent negative findings on causality between Lp(a) and T2D by employing the Mendelian randomization (MR) approach using cross-sectional data from three independent cohorts, Berlin Aging Study II (BASE-II; n = 2012), LIFE-Adult (n = 3281) and LIFE-Heart (n = 2816)...
September 2, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28856502/mendelian-randomization-analysis-indicates-serum-urate-has-a-causal-effect-on-renal-function-in-chinese-women
#8
Jing Liu, Hui Zhang, Zheng Dong, Jingru Zhou, Yanyun Ma, Yuan Li, Qiaoxia Qian, Ziyu Yuan, Juan Zhang, Yajun Yang, Xiaofeng Wang, Xingdong Chen, Hejian Zou, Li Jin, Jiucun Wang
PURPOSE: High levels of serum uric acid can predict the progression of stage I and II chronic kidney disease (CKD), but whether serum urate is an independent risk factor or has causal impact on serum creatinine (SCr) and renal function remains unclear. METHODS: Mendelian randomization was used to determine whether serum uric acid had a causal effect on renal function, represented by estimated glomerular filtration rate (eGFR), with potential confounding factors, in 3734 subjects from the Taizhou Longitudinal Study...
August 30, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28846118/association-of-genetic-variants-related-to-cetp-inhibitors-and-statins-with-lipoprotein-levels-and-cardiovascular-risk
#9
Brian A Ference, John J P Kastelein, Henry N Ginsberg, M John Chapman, Stephen J Nicholls, Kausik K Ray, Chris J Packard, Ulrich Laufs, Robert D Brook, Clare Oliver-Williams, Adam S Butterworth, John Danesh, George Davey Smith, Alberico L Catapano, Marc S Sabatine
Importance: Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered. Objective: To estimate the association between changes in levels of LDL-C (and other lipoproteins) and the risk of cardiovascular events related to variants in the CETP gene, both alone and in combination with variants in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene...
September 12, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28835472/dissecting-causal-pathways-using-mendelian-randomization-with-summarized-genetic-data-application-to-age-at-menarche-and-risk-of-breast-cancer
#10
Stephen Burgess, Deborah J Thompson, Jessica M B Rees, Felix R Day, John R Perry, Ken K Ong
Mendelian randomization is the use of genetic variants as instrumental variables to estimate causal effects of risk factors on outcomes. The total causal effect of a risk factor is the change in the outcome resulting from intervening on the risk factor. This total causal effect may potentially encompass multiple mediating mechanisms. For a proposed mediator, the direct effect of the risk factor is the change in the outcome resulting from a change in the risk factor keeping the mediator constant. A difference between the total effect and the direct effect indicates that the causal pathway from the risk factor to the outcome acts at least in part via the mediator (an indirect effect)...
August 23, 2017: Genetics
https://www.readbyqxmd.com/read/28834162/whither-the-genotype-phenotype-relationship-an-historical-and-methodological-appraisal
#11
Gene S Fisch
More than a century ago, Wilhelm Johannsen proposed the terms "genotype" and "phenotype" to study heredity. Much of what we know about genetics and behavior has evolved since then, especially how causality from genotypes can be inferred from observational studies of phenotypes. Unfortunately, there are genotypes that produce complex clinical-behavioral phenotypes-pleiotropy. In addition, there are often many genotypes that produce the same phenotype, adding a layer of complexity in establishing valid genotype-phenotype relationships...
September 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28821713/evaluating-the-causal-relation-of-apoa-iv-with-disease-related-traits-a-bidirectional-two-sample-mendelian-randomization-study
#12
Salome Mack, Stefan Coassin, Julien Vaucher, Florian Kronenberg, Claudia Lamina
Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly available summary-level datasets from GWAS consortia on apoA-IV concentrations (n = 13,813), kidney function (estimated glomerular filtration rate (eGFR), n = 133,413), lipid traits (HDL cholesterol, LDL cholesterol, triglycerides, n = 188,577), adiposity-related traits (body-mass-index (n = 322,206), waist-hip-ratio (n = 210,088)) and fasting glucose (n = 133,010)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820869/necrotizing-enterocolitis-and-high-intestinal-iron-uptake-due-to-genetic-variants
#13
Wolfgang Göpel, Josephine Drese, Tanja K Rausch, Nele Twisselmann, Bettina Bohnhorst, Andreas Müller, Axel Franz, Andreas Ziegler, Christoph Härtel, Egbert Herting
BACKGROUND: Intestinal iron is a nutritional compound, which is essential for enteric microbiota. We evaluated the hypothesis that polymorphisms which are known modifiers of intestinal iron uptake in adults are associated with necrotizing enterocolitis (NEC) in preterm infants. METHODS: Preterm infants (birth weight below 1,500 grams) were studied. Single nucleotide polymorphisms with known effects on serum iron levels (rs1800562, rs1799945, rs855791) were determined by polymerase chain reaction...
August 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28819171/thyroid-function-and-ischemic-heart-disease-a-mendelian-randomization-study
#14
Jie V Zhao, C Mary Schooling
To clarify the role of thyroid function in ischemic heart disease (IHD) we assessed IHD risk and risk factors according to genetically predicted thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) positivity. Separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used in an extensively genotyped case (n = 64,374)-control (n = 130,681) study, CARDIoGRAMplusC4D. Associations with lipids, diabetes and adiposity were assessed using the Global Lipids Genetics Consortium Results (n = 196,475), the DIAbetes Genetics Replication And Meta-analysis case (n = 34,380)-control (n = 114,981) study, and the Genetic Investigation of ANthropometric Traits (body mass index in 152,893 men and 171,977 women, waist-hip ratio in 93,480 men and 116,741 women)...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819125/inflammation-and-bone-mineral-density-a-mendelian-randomization-study
#15
Jian V Huang, C Mary Schooling
Osteoporosis is a common age-related disorder leading to an increase in osteoporotic fractures and resulting in significant suffering and disability. Inflammation may contribute to osteoporosis, as it does to many other chronic diseases. We examined whether inflammation is etiologically relevant to osteoporosis, assessed from bone mineral density (BMD), as a new potential target of intervention, or whether it is a symptom/biomarker of osteoporosis. We obtained genetic predictors of inflammatory markers from genome-wide association studies and applied them to a large genome wide association study of BMD...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812575/response-to-challenge-in-interpretation-of-mendelian-randomization-studies-using-lactase-persistence-as-instrumental-variable
#16
Q Yang, C M Schooling
No abstract text is available yet for this article.
August 16, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28812574/challenge-in-interpretation-of-mendelian-randomization-studies-using-lactase-persistence-as-instrumental-variable
#17
L E T Vissers, Y T van der Schouw, I Sluijs
No abstract text is available yet for this article.
August 16, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28797893/genetic-association-of-telomere-length-with-hepatocellular-carcinoma-risk-a-mendelian-randomization-analysis
#18
Yue Cheng, Chengxiao Yu, Mingtao Huang, Fangzhi Du, Ci Song, Zijian Ma, Xiangjun Zhai, Yuan Yang, Jibin Liu, Jin-Xin Bei, Weihua Jia, Guangfu Jin, Shengping Li, Weiping Zhou, Jianjun Liu, Juncheng Dai, Zhibin Hu
BACKGROUND: Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. METHODS: Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls)...
August 7, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28797570/genetic-variants-related-to-longer-telomere-length-are-associated-with-increased-risk-of-renal-cell-carcinoma
#19
Mitchell J Machiela, Jonathan N Hofmann, Robert Carreras-Torres, Kevin M Brown, Mattias Johansson, Zhaoming Wang, Matthieu Foll, Peng Li, Nathaniel Rothman, Sharon A Savage, Valerie Gaborieau, James D McKay, Yuanqing Ye, Marc Henrion, Fiona Bruinsma, Susan Jordan, Gianluca Severi, Kristian Hveem, Lars J Vatten, Tony Fletcher, Kvetoslava Koppova, Susanna C Larsson, Alicja Wolk, Rosamonde E Banks, Peter J Selby, Douglas F Easton, Paul Pharoah, Gabriella Andreotti, Laura E Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Mannisto, Stephanie Weinstein, Peter E Clark, Todd E Edwards, Loren Lipworth, Susan M Gapstur, Victoria L Stevens, Hallie Carol, Matthew L Freedman, Mark M Pomerantz, Eunyoung Cho, Peter Kraft, Mark A Preston, Kathryn M Wilson, J Michael Gaziano, Howard S Sesso, Amanda Black, Neal D Freedman, Wen-Yi Huang, John G Anema, Richard J Kahnoski, Brian R Lane, Sabrina L Noyes, David Petillo, Leandro M Colli, Joshua N Sampson, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Egor Prokhortchouk, Konstantin G Skryabin, Meredith Yeager, Mirjana Mijuskovic, Miodrag Ognjanovic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, H Bas Bueno-de-Mesquita, Federico Canzian, Eric J Duell, Börje Ljungberg, Raviprakash T Sitaram, Ulrike Peters, Emily White, Garnet L Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E Moore, Christopher Wood, Timothy Eisen, James Larkin, Toni K Choueiri, G Mark Lathrop, Bin Tean Teh, Jean-Francois Deleuze, Xifeng Wu, Richard S Houlston, Paul Brennan, Stephen J Chanock, Ghislaine Scelo, Mark P Purdue
BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations...
August 7, 2017: European Urology
https://www.readbyqxmd.com/read/28795686/hdl-and-atherosclerotic-cardiovascular-disease-genetic-insights-into-complex-biology
#20
REVIEW
Robert S Rosenson, H Bryan Brewer, Philip J Barter, Johan L M Björkegren, M John Chapman, Daniel Gaudet, Daniel Seung Kim, Eric Niesor, Kerry-Anne Rye, Frank M Sacks, Jean-Claude Tardif, Robert A Hegele
Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants...
August 10, 2017: Nature Reviews. Cardiology
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