scholarly journals Mendelian randomisation with coarsened exposures

2020 ◽  
Author(s):  
Matthew J. Tudball ◽  
Jack Bowden ◽  
Rachael A. Hughes ◽  
Amanda Ly ◽  
Marcus R. Munafò ◽  
...  
Keyword(s):  
Genetic Variance ◽  
Epidemiological Studies ◽  
Simple Expression ◽  
Effect Sizes ◽  
Mendelian Randomisation ◽  
Exposure Measurement ◽  
Continuous Trait ◽  
The One ◽  
The Relationship ◽  
Genetic Instruments

AbstractA key assumption in Mendelian randomisation is that the relationship between the genetic instruments and the outcome is fully mediated by the exposure, known as the exclusion restriction assumption. However, in epidemiological studies, the exposure is often a coarsened approximation to some latent continuous trait. For example, latent liability to schizophrenia can be thought of as underlying the binary diagnosis measure. Genetically-driven variation in the outcome can exist within categories of the exposure measurement, thus violating this assumption. We propose a framework to clarify this violation, deriving a simple expression for the resulting bias and showing that it may inflate or deflate effect estimates but will not reverse their sign. We then characterise a set of assumptions and a straight-forward method for estimating the effect of standard deviation increases in the latent exposure. Our method relies on a sensitivity parameter which can be interpreted as the genetic variance of the latent exposure. We show that this method can be applied in both the one-sample and two-sample settings. We conclude by demonstrating our method in an applied example and re-analysing two papers which are likely to suffer from this type of bias, allowing meaningful interpretation of their effect sizes.

scholarly journals Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis

2021 ◽  
Author(s):  
Richard Culliford ◽  
Alex J. Cornish ◽  
Philip J. Law ◽  
Susan M. Farrington ◽  
Kimmo Palin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Causal Effect ◽  
Gallstone Disease ◽  
Epidemiological Studies ◽  
Mendelian Randomisation ◽  
Linear Relationships ◽  
Potential Risk Factors ◽  
The Relationship ◽  
Circulating Levels

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

scholarly journals The use of negative control outcomes in Mendelian Randomisation to detect potential population stratification or selection bias

2020 ◽  
Author(s):  
Eleanor Sanderson ◽  
Tom G Richardson ◽  
Gibran Hemani ◽  
George Davey Smith
Keyword(s):  
Selection Bias ◽  
Genetic Variants ◽  
Population Stratification ◽  
Epidemiological Studies ◽  
Negative Control ◽  
Mendelian Randomisation ◽  
Hair Colour ◽  
Potential Population ◽  
The Relationship ◽  
Mr Study

AbstractA key assumption of Mendelian randomisation (MR) analysis is that there is no association between the genetic variants used as instruments and the outcome other than through the exposure of interest. Two ways in which this assumption can be violated are through population stratification and selection bias which can introduce confounding of the relationship between the genetic variants and the outcome and so induce an association between them. Negative control outcomes are increasingly used to detect unobserved confounding in observational epidemiological studies. Here we consider the use of negative control outcomes in MR studies. As a negative control outcome in an MR study we propose the use of phenotypes which are determined before the exposure and outcome but which are likely to be subject to the same confounding as the exposure or outcome of interest. We illustrate our method with a two-sample MR analysis of a preselected set of exposures on self-reported tanning ability and hair colour. Our results show that, of the 33 exposures considered, GWAS studies of adiposity and education related traits are likely to be subject to population stratification and/or selection bias that is not controlled for through adjustment and so any MR study including these traits may be subject to bias that cannot be identified through standard pleiotropy robust methods.

scholarly journals The Association Between Body Mass Index (BMI) and Sleep Duration: Where Are We after nearly Two Decades of Epidemiological Research?

2019 ◽  
Vol 16 (22) ◽  
pp. 4327 ◽  
Author(s):  
Victoria Garfield
Keyword(s):  
Body Mass Index ◽  
Sleep Duration ◽  
Body Mass ◽  
Epidemiological Studies ◽  
Effect Sizes ◽  
Vast Number ◽  
The Past ◽  
Bidirectional Relationship ◽  
Near Future ◽  
The Relationship

Over the past twenty years we have seen a vast number of epidemiological studies emerge on the topic of obesity and sleep duration, with a focus on body mass index, as it is easy and cheap to measure and analyse. Such studies largely observe that cross-sectionally a higher BMI is associated with shorter sleep and that in longitudinal studies shorter sleep duration is associated with increases in BMI over time, but some research has found no relationship between the two. This narrative review is not exhaustive, but appraises the literature on sleep duration and BMI from perspectives that have previously been unexplored in a single paper. As such, I discuss research in these important areas: bidirectionality, objective vs. subjective sleep duration, how meaningful the effect sizes are and how we have begun to address causality in this area. From the evidence appraised in this review, it is clear that: (i) there is some modest evidence of a bidirectional relationship between BMI and sleep duration in both children and adults; (ii) objective measurements of sleep should be used where possible; (iii) it remains difficult to confirm whether the effect sizes are conclusively meaningful in a clinical setting, but at least in adults this so far seems unlikely; (iv) to date, there is no solid evidence that this relationship (in either direction) is in fact causal. In the near future, I would like to see triangulation of these findings and perhaps a move towards focusing on distinct aspects of the relationship between obesity and sleep that have not previously been addressed in detail, for various reasons.

scholarly journals Polycystic ovary syndrome metabolic and hormonal dysfunction in relation to osteoarthritis onset and development: innocent bystander or major risk factor?

2021 ◽  
pp. 40-51
Author(s):  
Tsvetoslav Georgiev ◽  
Plamena Kabakchieva
Keyword(s):  
Metabolic Disorders ◽  
Polycystic Ovary ◽  
Weight Bearing ◽  
Epidemiological Studies ◽  
Close Link ◽  
Hormonal Dysfunction ◽  
Comprehensive Search ◽  
The One ◽  
Prospective Longitudinal ◽  
The Relationship

The close link between osteoarthritis (OA) and metabolic disorders on the one hand and hormonal disorders on the other suggests a possible association between OA and endocrine-metabolic disorders, such as PCOS. The aim of this review is to analyze the relationship between PCOS and OA, to consider the common pathogenetic mechanisms between the two conditions, and to summarize the data accumulated so far in the literature. For the purposes of our narrative review, a comprehensive search was conducted within credible databases. Our literature search found that epidemiological studies have shown a higher incidence of knee and hip OA in women with PCOS. This can be partly explained by obesity, which is a common intersection between the two conditions. Potential mechanisms among OA, PCOS, and obesity were considered. Another common point between OA and PCOS is that both conditions can be considered as highly heterogeneous syndromes with various etiologies, the result of a combination of systemic (genetic, hormonal, and metabolic) and local factors. To date, hyperandrogenism and greater cartilage thickness in young women with PCOS remain unclear in terms of determining the risk of developing OA. Prospective longitudinal studies are needed to assess the “fate” of the weight-bearing joints in women with PCOS, who are more likely to suffer from knee joint complaints.

Misreading Egypt

2018 ◽  
Author(s):  
Jesse Schotter
Keyword(s):  
New Media ◽  
Narrative Form ◽  
Experimental Film ◽  
Tower Of Babel ◽  
Avant Garde ◽  
Sergei Eisenstein ◽  
History Of ◽  
The One ◽  
The Relationship ◽  
Modern Technologies

The first chapter of Hieroglyphic Modernisms exposes the complex history of Western misconceptions of Egyptian writing from antiquity to the present. Hieroglyphs bridge the gap between modern technologies and the ancient past, looking forward to the rise of new media and backward to the dispersal of languages in the mythical moment of the Tower of Babel. The contradictory ways in which hieroglyphs were interpreted in the West come to shape the differing ways that modernist writers and filmmakers understood the relationship between writing, film, and other new media. On the one hand, poets like Ezra Pound and film theorists like Vachel Lindsay and Sergei Eisenstein use the visual languages of China and of Egypt as a more primal or direct alternative to written words. But Freud, Proust, and the later Eisenstein conversely emphasize the phonetic qualities of Egyptian writing, its similarity to alphabetical scripts. The chapter concludes by arguing that even avant-garde invocations of hieroglyphics depend on narrative form through an examination of Hollis Frampton’s experimental film Zorns Lemma.

Researching (with) Major Food Retailers

2015 ◽  
Vol 15 (3) ◽  
pp. 33-39 ◽  
Author(s):  
David Evans
Keyword(s):  
Food Systems ◽  
Academic Research ◽  
Social Scientists ◽  
Major Food ◽  
Food Retailers ◽  
Food Retailer ◽  
The One ◽  
The Uk ◽  
The Relationship ◽  
Opening Up

This paper considers the relationship between social science and the food industry, and it suggests that collaboration can be intellectually productive and morally rewarding. It explores the middle ground that exists between paid consultancy models of collaboration on the one hand and a principled stance of nonengagement on the other. Drawing on recent experiences of researching with a major food retailer in the UK, I discuss the ways in which collaborating with retailers can open up opportunities for accessing data that might not otherwise be available to social scientists. Additionally, I put forward the argument that researchers with an interest in the sustainability—ecological or otherwise—of food systems, especially those of a critical persuasion, ought to be empirically engaging with food businesses. I suggest that this is important in terms of generating better understandings of the objectionable arrangements that they seek to critique, and in terms of opening up conduits through which to affect positive changes. Cutting across these points is the claim that while resistance to commercial engagement might be misguided, it is nevertheless important to acknowledge the power-geometries of collaboration and to find ways of leveling and/or leveraging them. To conclude, I suggest that universities have an important institutional role to play in defining the terms of engagement as well as maintaining the boundaries between scholarship and consultancy—a line that can otherwise become quite fuzzy when the worlds of commerce and academic research collide.

Choice Of Technique And The Volume Of Saving (A Re-Examination Of The Cobb-Douglas Model)

1968 ◽  
Vol 8 (4) ◽  
pp. 606-617
Author(s):  
Mohammad Anisur Rahman
Keyword(s):  
Economic Development ◽  
Production Function ◽  
Development Policy ◽  
Social Goals ◽  
The Other ◽  
Economic Development Policy ◽  
Labour Intensity ◽  
The One ◽  
Choice Of Technique ◽  
The Relationship

The purpose of this paper is to re-examine the relationship between the degree of aggregate labour-intensity and the aggregate volume of saving in an economy where a Cobb-6ouglas production function in its traditional form can be assumed to give a good approximation to reality. The relationship in ques¬tion has an obviously important bearing on economic development policy in the area of choice of labour intensity. To the extent that and in the range where an increase in labour intensity would adversely affect the volume of savings, a con¬flict arises between two important social objectives, i.e., higher rate of capital formation on the one hand and greater employment and distributive equity on the other. If relative resource endowments in the economy are such that such a "competitive" range of labour-intensity falls within the nation's attainable range of choice, development planners will have to arrive at a compromise between these two social goals.

Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure

2018 ◽  
Vol 24 (3) ◽  
pp. 341-358 ◽  
Author(s):  
Xiaotong Ji ◽  
Yingying Zhang ◽  
Guangke Li ◽  
Nan Sang
Keyword(s):  
Heart Failure ◽  
Particulate Matter ◽  
Inflammatory Response ◽  
Heart Diseases ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Inflammatory Mechanism ◽  
High Concentrations ◽  
Future Work ◽  
The Relationship

Recently, numerous studies have found that particulate matter (PM) exposure is correlated with increased hospitalization and mortality from heart failure (HF). In addition to problems with circulation, HF patients often display high expression of cytokines in the failing heart. Thus, as a recurring heart problem, HF is thought to be a disorder characterized in part by the inflammatory response. In this review, we intend to discuss the relationship between PM exposure and HF that is based on inflammatory mechanism and to provide a comprehensive, updated evaluation of the related studies. Epidemiological studies on PM-induced heart diseases are focused on high concentrations of PM, high pollutant load exposure in winter, or susceptible groups with heart diseases, etc. Furthermore, it appears that the relationship between fine or ultrafine PM and HF is stronger than that between HF and coarse PM. However, fewer studies paid attention to PM components. As for experimental studies, it is worth noting that coarse PM may indirectly promote the inflammatory response in the heart through systematic circulation of cytokines produced primarily in the lungs, while ultrafine PM and its components can enter circulation and further induce inflammation directly in the heart. In terms of PM exposure and enhanced inflammation during the pathogenesis of HF, this article reviews the following mechanisms: hemodynamics, oxidative stress, Toll-like receptors (TLRs) and epigenetic regulation. However, many problems are still unsolved, and future work will be needed to clarify the complex biologic mechanisms and to identify the specific components of PM responsible for adverse effects on heart health.

Adolescent smoking behavior and communication with parents: Depression as a mediator and gender as a moderator

2019 ◽  
Vol 47 (10) ◽  
pp. 1-9 ◽  
Author(s):  
Xieping Chen ◽  
Qian Xie ◽  
Yuting Yang
Keyword(s):  
Smoking Behavior ◽  
Depression Scale ◽  
Epidemiological Studies ◽  
Adolescent Smoking ◽  
Junior High Schools ◽  
Test Results ◽  
Negative Effect ◽  
And Gender ◽  
The Relationship ◽  
Communication Scale

Parent–adolescent communication is assumed to be an important factor affecting adolescent smoking behavior. However, the inner mechanism accounting for this association has still not been clarified in research. Our purpose in this study was to examine the relationships between parent–adolescent communication, adolescent smoking behavior, and depression, as well as gender differences in the relationship between depression and adolescent smoking behavior. Participants were 1,134 students at 6 junior high schools in China who completed the Parent-Adolescent Communication Scale, the Epidemiological Studies Depression Scale, and the Smoking Behavior Test. Results showed that parent-adolescent communication had a significant negative effect on adolescent smoking behavior and depression partially mediated the relationship between parent–adolescent communication and adolescent smoking behavior. In addition, gender moderated the relationship between depression and adolescent smoking behavior. Overall, these findings may help to promote better understanding of the relationship between parent–adolescent communication and adolescent smoking behavior.

Bastard Feudalism and the Framing of Thirteenth-Century England

2018 ◽  
Author(s):  
Peter Coss
Keyword(s):  
Middle Ages ◽  
Thirteenth Century ◽  
Twelfth Century ◽  
The State ◽  
The Other ◽  
Great Work ◽  
Early Middle Ages ◽  
The One ◽  
The Relationship

In the introduction to his great work of 2005, Framing the Early Middle Ages, Chris Wickham urged not only the necessity of carefully framing our studies at the outset but also the importance of closely defining the words and concepts that we employ, the avoidance ‘cultural sollipsism’ wherever possible and the need to pay particular attention to continuities and discontinuities. Chris has, of course, followed these precepts on a vast scale. My aim in this chapter is a modest one. I aim to review the framing of thirteenth-century England in terms of two only of Chris’s themes: the aristocracy and the state—and even then primarily in terms of the relationship between the two. By the thirteenth century I mean a long thirteenth century stretching from the period of the Angevin reforms of the later twelfth century on the one hand to the early to mid-fourteenth on the other; the reasons for taking this span will, I hope, become clearer during the course of the chapter, but few would doubt that it has a validity.

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