This article considers the relationships between consumption, the environment, and wider sociological endeavour. The current vogue for applying theories of practice to the policy domain of ...‘sustainable consumption’ has been generative of conceptual renewal, however the field now sits closer to the applied environmental social sciences than to the sociology of consumption. The analysis proceeds via a close reading of the intellectual currents that have given rise to this situation, and it identifies a number of interrelated issues concerning conceptual slippage and the exclusion of core disciplinary concerns. Accordingly a more suitable definition of consumption is offered, an agenda for re-engaging with foundational approaches to consumer culture is established, and a renewal and reorientation of critique is proposed. Working through and building on the contributions of practice theoretical repertoires, this article suggests that consumption scholarship offers a distinctive set of resources to discussions of current ecological crises and uncertain social futures. These are briefly described and the conclusion argues that consumption still matters.
Mendelian randomization (MR) is an approach that uses genetic variants associated with a modifiable exposure or biological intermediate to estimate the causal relationship between these variables and ...a medically relevant outcome. Although it was initially developed to examine the relationship between modifiable exposures biomarkers and disease, its use has expanded to encompass applications in molecular epidemiology, systems biology, pharmacogenomics, and many other areas. The purpose of this review is to introduce MR, the principles behind the approach, and its limitations. We consider some of the new applications of the methodology, including informing drug development, and comment on some promising extensions, including two-step, two-sample, and bidirectional MR. We show how these new methods can be combined to efficiently examine causality in complex biological networks and provide a new framework to data mine high-dimensional studies as we transition into the age of hypothesis-free causality.
Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor ...subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.
Large-scale cross-sectional and cohort studies have transformed our understanding of the genetic and environmental determinants of health outcomes. However, the representativeness of these samples ...may be limited-either through selection into studies, or by attrition from studies over time. Here we explore the potential impact of this selection bias on results obtained from these studies, from the perspective that this amounts to conditioning on a collider (i.e. a form of collider bias). Whereas it is acknowledged that selection bias will have a strong effect on representativeness and prevalence estimates, it is often assumed that it should not have a strong impact on estimates of associations. We argue that because selection can induce collider bias (which occurs when two variables independently influence a third variable, and that third variable is conditioned upon), selection can lead to substantially biased estimates of associations. In particular, selection related to phenotypes can bias associations with genetic variants associated with those phenotypes. In simulations, we show that even modest influences on selection into, or attrition from, a study can generate biased and potentially misleading estimates of both phenotypic and genotypic associations. Our results highlight the value of knowing which population your study sample is representative of. If the factors influencing selection and attrition are known, they can be adjusted for. For example, having DNA available on most participants in a birth cohort study offers the possibility of investigating the extent to which polygenic scores predict subsequent participation, which in turn would enable sensitivity analyses of the extent to which bias might distort estimates.
This paper advances geographical perspectives on household sustainability by extending the range of insights from consumption scholarship that are brought to bear on the issue. Research that links ...consumption to the dynamics of variously sustainable practices currently dominate, resulting in a particular and partial reading of material culture. I suggest that geographical approaches to the social life of things may yield new insights into materiality and household sustainability. Specifically, I argue that “following the thing” – which is typically focused on commodity chains – could usefully be extended into people's homes. This is not introduced as a way to acknowledge the connections between points in a network, rather, it is positioned as a set of theoretical and methodological resources that can be utilised to explore the movement and placing of things as they move through a critical juncture – in this case the household. To illustrate, I present material drawn from two empirical studies of households in the UK. The first is an ethnographically‐informed study of how food becomes waste; the second is a quantitative survey of laundry habits. Attention is paid to the ways in which the ongoing categorisation and valuation of things shape their trajectories and move them in directions that give rise to (adverse) environmental impacts. To conclude I sketch out an agenda for future studies, consider how a focus on households can yield more comprehensive biographies of things, and address the implications of this analysis both for consumption scholarship and for engagement with sustainability research and policy beyond human geography.
Results from genome-wide association studies (GWAS) can be used to infer causal relationships between phenotypes, using a strategy known as 2-sample Mendelian randomization (2SMR) and bypassing the ...need for individual-level data. However, 2SMR methods are evolving rapidly and GWAS results are often insufficiently curated, undermining efficient implementation of the approach. We therefore developed MR-Base (<ext-link ext-link-type="uri" xlink:href="http://www.mrbase.org">http://www.mrbase.org</ext-link>): a platform that integrates a curated database of complete GWAS results (no restrictions according to statistical significance) with an application programming interface, web app and R packages that automate 2SMR. The software includes several sensitivity analyses for assessing the impact of horizontal pleiotropy and other violations of assumptions. The database currently comprises 11 billion single nucleotide polymorphism-trait associations from 1673 GWAS and is updated on a regular basis. Integrating data with software ensures more rigorous application of hypothesis-driven analyses and allows millions of potential causal relationships to be efficiently evaluated in phenome-wide association studies.
Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric ...symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.
Estimating effects of parental and sibling genotypes (indirect genetic effects) can provide insight into how the family environment influences phenotypic variation. There is growing molecular genetic ...evidence for effects of parental phenotypes on their offspring (e.g. parental educational attainment), but the extent to which siblings affect each other is currently unclear. Here we used data from samples of unrelated individuals, without (singletons) and with biological full-siblings (non-singletons), to investigate and estimate sibling effects. Indirect genetic effects of siblings increase (or decrease) the covariance between genetic variation and a phenotype. It follows that differences in genetic association estimates between singletons and non-singletons could indicate indirect genetic effects of siblings if there is no heterogeneity in other sources of genetic association between singletons and non-singletons. We used UK Biobank data to estimate polygenic score (PGS) associations for height, BMI and educational attainment in self-reported singletons (N = 50,143) and non-singletons (N = 328,549). The educational attainment PGS association estimate was 12% larger (95% C.I. 3%, 21%) in the non-singleton sample than in the singleton sample, but the height and BMI PGS associations were consistent. Birth order data suggested that the difference in educational attainment PGS associations was driven by individuals with older siblings rather than firstborns. The relationship between number of siblings and educational attainment PGS associations was non-linear; PGS associations were 24% smaller in individuals with 6 or more siblings compared to the rest of the sample (95% C.I. 11%, 38%). We estimate that a 1 SD increase in sibling educational attainment PGS corresponds to a 0.025 year increase in the index individual's years in schooling (95% C.I. 0.013, 0.036). Our results suggest that older siblings may influence the educational attainment of younger siblings, adding to the growing evidence that effects of the environment on phenotypic variation partially reflect social effects of germline genetic variation in relatives.
The influence of genetic variation on complex diseases is potentially mediated through a range of highly dynamic epigenetic processes exhibiting temporal variation during development and later life. ...Here we present a catalogue of the genetic influences on DNA methylation (methylation quantitative trait loci (mQTL)) at five different life stages in human blood: children at birth, childhood, adolescence and their mothers during pregnancy and middle age.
We show that genetic effects on methylation are highly stable across the life course and that developmental change in the genetic contribution to variation in methylation occurs primarily through increases in environmental or stochastic effects. Though we map a large proportion of the cis-acting genetic variation, a much larger component of genetic effects influencing methylation are acting in trans. However, only 7 % of discovered mQTL are trans-effects, suggesting that the trans component is highly polygenic. Finally, we estimate the contribution of mQTL to variation in complex traits and infer that methylation may have a causal role consistent with an infinitesimal model in which many methylation sites each have a small influence, amounting to a large overall contribution.
DNA methylation contains a significant heritable component that remains consistent across the lifespan. Our results suggest that the genetic component of methylation may have a causal role in complex traits. The database of mQTL presented here provide a rich resource for those interested in investigating the role of methylation in disease.
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