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https://www.readbyqxmd.com/read/28317167/semiparametric-methods-for-estimation-of-a-nonlinear-exposure-outcome-relationship-using-instrumental-variables-with-application-to-mendelian-randomization
#1
James R Staley, Stephen Burgess
Mendelian randomization, the use of genetic variants as instrumental variables (IV), can test for and estimate the causal effect of an exposure on an outcome. Most IV methods assume that the function relating the exposure to the expected value of the outcome (the exposure-outcome relationship) is linear. However, in practice, this assumption may not hold. Indeed, often the primary question of interest is to assess the shape of this relationship. We present two novel IV methods for investigating the shape of the exposure-outcome relationship: a fractional polynomial method and a piecewise linear method...
March 20, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28302601/dairy-consumption-systolic-blood-pressure-and-risk-of-hypertension-mendelian-randomization-study
#2
Ming Ding, Tao Huang, Helle Km Bergholdt, Børge G Nordestgaard, Christina Ellervik, Lu Qi
Objective To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal.Design Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.Setting CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.Participants Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis...
March 16, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28298470/genetically-driven-hyperglycemia-increases-risk-of-coronary-artery-disease-separately-from-type-2-diabetes
#3
Jordi Merino, Aaron Leong, Daniel C Posner, Bianca Porneala, Lluís Masana, Josée Dupuis, Jose C Florez
OBJECTIVE: This study tested the hypothesis that genetically raised hyperglycemia increases coronary artery disease (CAD) risk separately from the risk conferred by type 2 diabetes as a whole. RESEARCH DESIGN AND METHODS: We conducted a Mendelian randomization (MR) analysis using summary-level statistics from the largest published meta-analyses of genome-wide association studies (GWAS) for fasting glucose (FG) (n = 133,010 participants free of diabetes) and CAD (n = 63,746 case subjects and 130,681 control subjects) of predominantly European ancestry...
March 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28250574/interleukin-6-trans-signaling-and-ischemic-vascular-disease-the-important-role-of-soluble-gp130
#4
REVIEW
Mario Luca Morieri, Angelina Passaro, Giovanni Zuliani
Inflammation plays a major role in the onset of cardiovascular disease (CVD). Interleukine-6 (IL-6) is a multifunctional cytokine involved both in the beneficial acute inflammatory response and in the detrimental chronic low-grade systemic inflammation. Large genetic human studies, using Mendelian randomization approaches, have clearly showed that IL-6 pathway is causally involved in the onset of myocardial infarction. At the same time, IL-6 pathway is divided into two arms: classic signaling (effective in hepatocytes and leukocytes) and trans-signaling (with ubiquitous activity)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28250266/clinical-perspectives-of-genetic-analyses-on-dyslipidemia-and-coronary-artery-disease
#5
Hayato Tada, Masa-Aki Kawashiri, Masakazu Yamagishi
We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from various aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets...
February 28, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28241208/association-between-telomere-length-and-risk-of-cancer-and-non-neoplastic-diseases-a-mendelian-randomization-study
#6
Philip C Haycock, Stephen Burgess, Aayah Nounu, Jie Zheng, George N Okoli, Jack Bowden, Kaitlin Hazel Wade, Nicholas J Timpson, David M Evans, Peter Willeit, Abraham Aviv, Tom R Gaunt, Gibran Hemani, Massimo Mangino, Hayley Patricia Ellis, Kathreena M Kurian, Karen A Pooley, Rosalind A Eeles, Jeffrey E Lee, Shenying Fang, Wei V Chen, Matthew H Law, Lisa M Bowdler, Mark M Iles, Qiong Yang, Bradford B Worrall, Hugh Stephen Markus, Rayjean J Hung, Chris I Amos, Amanda B Spurdle, Deborah J Thompson, Tracy A O'Mara, Brian Wolpin, Laufey Amundadottir, Rachael Stolzenberg-Solomon, Antonia Trichopoulou, N Charlotte Onland-Moret, Eiliv Lund, Eric J Duell, Federico Canzian, Gianluca Severi, Kim Overvad, Marc J Gunter, Rosario Tumino, Ulrika Svenson, Andre van Rij, Annette F Baas, Matthew J Bown, Nilesh J Samani, Femke N G van t'Hof, Gerard Tromp, Gregory T Jones, Helena Kuivaniemi, James R Elmore, Mattias Johansson, James Mckay, Ghislaine Scelo, Robert Carreras-Torres, Valerie Gaborieau, Paul Brennan, Paige M Bracci, Rachel E Neale, Sara H Olson, Steven Gallinger, Donghui Li, Gloria M Petersen, Harvey A Risch, Alison P Klein, Jiali Han, Christian C Abnet, Neal D Freedman, Philip R Taylor, John M Maris, Katja K Aben, Lambertus A Kiemeney, Sita H Vermeulen, John K Wiencke, Kyle M Walsh, Margaret Wrensch, Terri Rice, Clare Turnbull, Kevin Litchfield, Lavinia Paternoster, Marie Standl, Gonçalo R Abecasis, John Paul SanGiovanni, Yong Li, Vladan Mijatovic, Yadav Sapkota, Siew-Kee Low, Krina T Zondervan, Grant W Montgomery, Dale R Nyholt, David A van Heel, Karen Hunt, Dan E Arking, Foram N Ashar, Nona Sotoodehnia, Daniel Woo, Jonathan Rosand, Mary E Comeau, W Mark Brown, Edwin K Silverman, John E Hokanson, Michael H Cho, Jennie Hui, Manuel A Ferreira, Philip J Thompson, Alanna C Morrison, Janine F Felix, Nicholas L Smith, Angela M Christiano, Lynn Petukhova, Regina C Betz, Xing Fan, Xuejun Zhang, Caihong Zhu, Carl D Langefeld, Susan D Thompson, Feijie Wang, Xu Lin, David A Schwartz, Tasha Fingerlin, Jerome I Rotter, Mary Frances Cotch, Richard A Jensen, Matthias Munz, Henrik Dommisch, Arne S Schaefer, Fang Han, Hanna M Ollila, Ryan P Hillary, Omar Albagha, Stuart H Ralston, Chenjie Zeng, Wei Zheng, Xiao-Ou Shu, Andre Reis, Steffen Uebe, Ulrike Hüffmeier, Yoshiya Kawamura, Takeshi Otowa, Tsukasa Sasaki, Martin Lloyd Hibberd, Sonia Davila, Gang Xie, Katherine Siminovitch, Jin-Xin Bei, Yi-Xin Zeng, Asta Försti, Bowang Chen, Stefano Landi, Andre Franke, Annegret Fischer, David Ellinghaus, Carlos Flores, Imre Noth, Shwu-Fan Ma, Jia Nee Foo, Jianjun Liu, Jong-Won Kim, David G Cox, Olivier Delattre, Olivier Mirabeau, Christine F Skibola, Clara S Tang, Merce Garcia-Barcelo, Kai-Ping Chang, Wen-Hui Su, Yu-Sun Chang, Nicholas G Martin, Scott Gordon, Tracey D Wade, Chaeyoung Lee, Michiaki Kubo, Pei-Chieng Cha, Yusuke Nakamura, Daniel Levy, Masayuki Kimura, Shih-Jen Hwang, Steven Hunt, Tim Spector, Nicole Soranzo, Ani W Manichaikul, R Graham Barr, Bratati Kahali, Elizabeth Speliotes, Laura M Yerges-Armstrong, Ching-Yu Cheng, Jost B Jonas, Tien Yin Wong, Isabella Fogh, Kuang Lin, John F Powell, Kenneth Rice, Caroline L Relton, Richard M Martin, George Davey Smith
Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015...
February 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28238338/the-serum-uric-acid-concentration-is-not-causally-linked-to-diabetic-nephropathy-in-type-1-diabetes
#7
Aila J Ahola, Niina Sandholm, Carol Forsblom, Valma Harjutsalo, Emma Dahlström, Per-Henrik Groop
Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score...
February 18, 2017: Kidney International
https://www.readbyqxmd.com/read/28228143/relationship-between-salivary-pancreatic-amylase-and-body-mass-index-a-systems-biology-approach
#8
Amélie Bonnefond, Loïc Yengo, Aurélie Dechaume, Mickaël Canouil, Maxime Castelain, Estelle Roger, Frédéric Allegaert, Robert Caiazzo, Violeta Raverdy, Marie Pigeyre, Abdelilah Arredouani, Jean-Michel Borys, Claire Lévy-Marchal, Jacques Weill, Ronan Roussel, Beverley Balkau, Michel Marre, François Pattou, Thierry Brousseau, Philippe Froguel
BACKGROUND: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach. METHODS: We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D...
February 23, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28225053/genetically-predicted-milk-consumption-and-bone-health-ischemic-heart-disease-and-type-2-diabetes-a-mendelian-randomization-study
#9
Q Yang, S L Lin, S L Au Yeung, M K Kwok, L Xu, G M Leung, C M Schooling
BACKGROUND/OBJECTIVES: Milk provides protein and micronutrients, and is recommended by some dietary guidelines, particularly for bone health. Meta-analysis of small randomized controlled trials suggests that milk may increase bone mineral density, but they are very heterogeneous. No randomized controlled trial has assessed the effects of milk on major chronic diseases. Previous Mendelian randomization studies of milk did not consider bone health, found no effects on ischemic heart disease (IHD) or type 2 diabetes (T2D) but higher body mass index...
February 22, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28223712/insight-into-rheumatological-cause-and-effect-through-the-use-of-mendelian-randomization
#10
Philip C Robinson, Hyon K Choi, Ron Do, Tony R Merriman
No abstract text is available yet for this article.
February 22, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28223688/sequence-variant-at-8q24-21-associates-with-sciatica-caused-by-lumbar-disc-herniation
#11
Gyda Bjornsdottir, Stefania Benonisdottir, Gardar Sveinbjornsson, Unnur Styrkarsdottir, Gudmar Thorleifsson, G Bragi Walters, Aron Bjornsson, Ingvar H Olafsson, Elfar Ulfarsson, Arnor Vikingsson, Ragnheidur Hansdottir, Karl O Karlsson, Thorunn Rafnar, Ingileif Jonsdottir, Michael L Frigge, Augustine Kong, Asmundur Oddsson, Gisli Masson, Olafur T Magnusson, Tomas Gudbjartsson, Hreinn Stefansson, Patrick Sulem, Daniel Gudbjartsson, Unnur Thorsteinsdottir, Thorgeir E Thorgeirsson, Kari Stefansson
Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10(-12)) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28223325/mendelian-randomization-using-natural-genetic-variation-to-assess-the-causal-role-of-modifiable-risk-factors-in-observational-studies
#12
EDITORIAL
Ian J Neeland, Julia Kozlitina
No abstract text is available yet for this article.
February 21, 2017: Circulation
https://www.readbyqxmd.com/read/28219152/-mendelian-randomization-analysis-of-the-relationship-between-obesity-and-dna-methylation
#13
Y Gao, B Q Wang, W J Gao, W H Cao, C Q Yu, J Lyu, S F Wang, Z C Pang, L M Cong, H Wang, X P Wu, L M Liang, L M Li
Objective: To explore the association between DNA methylation and body mass index (BMI) using Mendelian randomization analysis. Methods: A total of 469 participants were selected from the Chinese National Twin Registry in 2013, who were living in Shandong, Jiangsu, Zhejiang, and Sichuan provinces, and at least 18 years of age. A questionnaire survey and physical examination were conducted to collect demographic, clinical, and behavioral information. Peripheral blood cells were collected to detect genotype and methylation status...
February 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28212870/the-174-g-c-interleukin-6-gene-polymorphism-is-associated-with-angiographic-progression-of-coronary-artery-disease-in-a-4-year-period
#14
Konstantinos Toutouzas, Dimitrios Klettas, Nikolaos Anousakis-Vlachochristou, Konstantinos Melidis, Zeta Azilazian, Maria Asimomiti, Antonios Karanasos, Anastasios Spanos, Eleftherios Tsiamis, Petros Nihoyannopoulos, Dimitris Tousoulis
BACKGROUND: Inflammation is the key process underlying the clinical course of coronary artery disease (CAD). C-reactive protein (CRP) and interleukin-6 (IL-6) participate in the pathophysiology and act as biomarkers. We sought to examine whether known single nucleotide polymorphisms (SNPs) impact the progression of CAD, reflecting higher inflammatory activity. METHODS: We retrospectively evaluated coronary angiographies of patients with already established CAD who were re-investigated for stable/unstable angina after a time interval >12 months...
February 14, 2017: Hellenic Journal of Cardiology: HJC, Hellēnikē Kardiologikē Epitheōrēsē
https://www.readbyqxmd.com/read/28210975/alcohol-and-cardiovascular-disease-how-much-is-too-much
#15
REVIEW
Augustin Toma, Guillaume Paré, Darryl P Leong
PURPOSE OF REVIEW: Previous research suggests that low-moderate alcohol consumption may have cardioprotective effects, while heavy or binge-pattern drinking is harmful. New evidence and research methodology may inform safe thresholds of alcohol use. This review examines recent evidence regarding alcohol's effect on cardiovascular disease, with a special consideration of pattern, drink type, and total quantity. RECENT FINDINGS: New epidemiologic research confirms the potential harmful cardiovascular effects of heavy episodic alcohol use and does not support the previous observation that low-moderate alcohol use protects against stroke...
March 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28196256/genetic-association-of-waist-to-hip-ratio-with-cardiometabolic-traits-type-2-diabetes-and-coronary-heart-disease
#16
Connor A Emdin, Amit V Khera, Pradeep Natarajan, Derek Klarin, Seyedeh M Zekavat, Allan J Hsiao, Sekar Kathiresan
Importance: In observational studies, abdominal adiposity has been associated with type 2 diabetes and coronary heart disease (CHD). Whether these associations represent causal relationships remains uncertain. Objective: To test the association of a polygenic risk score for waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure, and glycemic phenotypes...
February 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28196238/when-will-mendelian-randomization-become-relevant-for-clinical-practice-and-public-health
#17
EDITORIAL
George Davey Smith, Lavinia Paternoster, Caroline Relton
No abstract text is available yet for this article.
February 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28195141/a-mendelian-randomization-study-of-the-effect-of-calcium-on-coronary-artery-disease-myocardial-infarction-and-their-risk-factors
#18
Lin Xu, Shi Lin Lin, C Mary Schooling
Meta-analyses of randomized controlled trials (RCTs) suggest calcium could have adverse effects on cardiovascular disease, although these findings are controversial. To clarify, we assessed whether people with genetically higher calcium had a higher risk of coronary artery disease (CAD), myocardial infarction (MI) and their risk factors. We used a two-sample Mendelian randomization study. We identified genetic variants (single nucleotide polymorphisms (SNPs)) that independently contributed to serum calcium at genome-wide significance which we applied to large extensively genotyped studies of CAD, MI, diabetes, lipids, glycaemic traits and adiposity to obtain unconfounded estimates, with body mass index (BMI) as a control outcome...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186534/serum-iron-level-and-kidney-function-a-mendelian-randomization-study
#19
Fabiola Del Greco M, Luisa Foco, Irene Pichler, Philipp Eller, Kathrin Eller, Beben Benyamin, John B Whitfield, Peter P Pramstaller, John R Thompson, Cristian Pattaro, Cosetta Minelli
No abstract text is available yet for this article.
February 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28157721/complexity-of-mechanisms-among-human-proprotein-convertase-subtilisin-kexin-type-9-variants
#20
Jacqueline S Dron, Robert A Hegele
PURPOSE OF REVIEW: There are many reports of human variants in proprotein convertase subtilisin-kexin type 9 (PCSK9) that are either gain-of-function (GOF) or loss-of-function (LOF), with downstream effects on LDL cholesterol and cardiovascular disease (CVD) risk. However, data on particular mechanisms have only been minimally curated. RECENT FINDINGS: GOF variants are individually ultrarare, affect all domains of the protein, act to reduce LDL receptor expression through several mechanisms, are a minor cause of familial hypercholesterolemia, have been reported mainly within families, have variable LDL cholesterol-raising effects, and are associated with increased CVD risk mainly through observational studies in families and small cohorts...
February 2, 2017: Current Opinion in Lipidology
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