scholarly journals Mendelian randomization: a premature burial?

2015 ◽  
Author(s):  
George Davey Smith
Keyword(s):  
Causal Inference ◽  
Empirical Research ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Recent Developments ◽  
Potential Applications

Mendelian randomization is a promising approach to help improve causal inference in observational studies, with widespread potential applications, including to prioritization of pharmacotherapeutic targets for evaluation in RCTs. From its initial proposal the limitations of Mendelian randomization approaches have been widely recognised and discussed, and recently Pickrell has reiterated these1. However this critique did not acknowledge recent developments in both methodological and empirical research, nor did it recognise many future opportunities for application of the Mendelian randomization approach. These issues are briefly reviewed here.

scholarly journals Mendelian randomization does not support serum calcium in prostate cancer risk

2018 ◽  
Author(s):  
James Yarmolinsky ◽  
Katie Berryman ◽  
Ryan Langdon ◽  
Carolina Bonilla ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Causal Inference ◽  
Serum Calcium ◽  
Observational Studies ◽  
Advanced Prostate Cancer ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
A Genome ◽  
Increased Risk

AbstractBackground: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies.Objective: We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.Design: A genetic instrument was constructed using 5 single nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (N ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI: 0.63-1.08; P=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI: 0.57-1.70; P=0.93).Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

scholarly journals Mendelian randomization: use of genetics to enable causal inference in observational studies

2010 ◽  
Vol 25 (5) ◽  
pp. 1394-1398 ◽  
Author(s):  
M. Verduijn ◽  
B. Siegerink ◽  
K. J. Jager ◽  
C. Zoccali ◽  
F. W. Dekker
Keyword(s):  
Causal Inference ◽  
Observational Studies ◽  
Mendelian Randomization

Recent Developments of Ambulatory Assessment Methods

2014 ◽  
Vol 25 (4) ◽  
pp. 279-287 ◽  
Author(s):  
Stefan Hey ◽  
Panagiota Anastasopoulou ◽  
André Bideaux ◽  
Wilhelm Stork
Keyword(s):  
Real Time ◽  
Information And Communication Technologies ◽  
New Technologies ◽  
Psychological Research ◽  
Ambulatory Assessment ◽  
Emotional States ◽  
Recent Developments ◽  
Potential Applications ◽  
Information And Communication ◽  
Physiological Sensors

Ambulatory assessment of emotional states as well as psychophysiological, cognitive and behavioral reactions constitutes an approach, which is increasingly being used in psychological research. Due to new developments in the field of information and communication technologies and an improved application of mobile physiological sensors, various new systems have been introduced. Methods of experience sampling allow to assess dynamic changes of subjective evaluations in real time and new sensor technologies permit a measurement of physiological responses. In addition, new technologies facilitate the interactive assessment of subjective, physiological, and behavioral data in real-time. Here, we describe these recent developments from the perspective of engineering science and discuss potential applications in the field of neuropsychology.

257-OR: High Glucose Levels and Risk of Vascular Diseases—Observational Studies and Mendelian Randomization Studies of the General Population

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 257-OR
Author(s):  
FRIDA EMANUELSSON ◽  
SARAH MAROTT ◽  
ANNE TYBJAERG-HANSEN ◽  
BØRGE GRØNNE NORDESTGAARD ◽  
MARIANNE BENN
Keyword(s):  
General Population ◽  
High Glucose ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Vascular Diseases ◽  
Glucose Levels

scholarly journals Nondegenerate Bright Solitons in Coupled Nonlinear Schrödinger Systems: Recent Developments on Optical Vector Solitons

Photonics ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 258
Author(s):  
S. Stalin ◽  
R. Ramakrishnan ◽  
M. Lakshmanan
Keyword(s):  
Propagation Constant ◽  
Short Wave ◽  
Nonlinear Phenomena ◽  
Bilinear Method ◽  
Nonlinear Schrödinger ◽  
Bright Solitons ◽  
Nonlinear Schrödinger Systems ◽  
Recent Developments ◽  
Potential Applications ◽  
Photorefractive Materials

Nonlinear dynamics of an optical pulse or a beam continue to be one of the active areas of research in the field of optical solitons. Especially, in multi-mode fibers or fiber arrays and photorefractive materials, the vector solitons display rich nonlinear phenomena. Due to their fascinating and intriguing novel properties, the theory of optical vector solitons has been developed considerably both from theoretical and experimental points of view leading to soliton-based promising potential applications. Mathematically, the dynamics of vector solitons can be understood from the framework of the coupled nonlinear Schrödinger (CNLS) family of equations. In the recent past, many types of vector solitons have been identified both in the integrable and non-integrable CNLS framework. In this article, we review some of the recent progress in understanding the dynamics of the so called nondegenerate vector bright solitons in nonlinear optics, where the fundamental soliton can have more than one propagation constant. We address this theme by considering the integrable two coupled nonlinear Schrödinger family of equations, namely the Manakov system, mixed 2-CNLS system (or focusing-defocusing CNLS system), coherently coupled nonlinear Schrödinger (CCNLS) system, generalized coupled nonlinear Schrödinger (GCNLS) system and two-component long-wave short-wave resonance interaction (LSRI) system. In these models, we discuss the existence of nondegenerate vector solitons and their associated novel multi-hump geometrical profile nature by deriving their analytical forms through the Hirota bilinear method. Then we reveal the novel collision properties of the nondegenerate solitons in the Manakov system as an example. The asymptotic analysis shows that the nondegenerate solitons, in general, undergo three types of elastic collisions without any energy redistribution among the modes. Furthermore, we show that the energy sharing collision exhibiting vector solitons arises as a special case of the newly reported nondegenerate vector solitons. Finally, we point out the possible further developments in this subject and potential applications.

scholarly journals Extracellular Vesicles: Novel Opportunities to Understand and Detect Neoplastic Diseases

2021 ◽  
pp. 030098582199932
Author(s):  
Laura Bongiovanni ◽  
Anneloes Andriessen ◽  
Marca H. M. Wauben ◽  
Esther N. M. Nolte-’t Hoen ◽  
Alain de Bruin
Keyword(s):  
Extracellular Vesicles ◽  
Biologically Active ◽  
Liquid Biopsies ◽  
Donor Cells ◽  
Recent Developments ◽  
Veterinary Pathology ◽  
Cell Components ◽  
Potential Applications ◽  
Intercellular Communications

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies.

Using Mendelian randomization as the cornerstone for causal inference in epidemiology

2021 ◽  
Author(s):  
Jianguo Xu ◽  
Muyang Li ◽  
Ya Gao ◽  
Ming Liu ◽  
Shuzhen Shi ◽  
...  
Keyword(s):  
Causal Inference ◽  
Mendelian Randomization

scholarly journals Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

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