Common SNPs explain a large proportion of the heritability for human height

SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.

The shared genetics of migraine and anxious depression

OBJECTIVES To investigate: - (1) whether shared genetic factors influence migraine and anxious depression; - (2) whether the genetic architecture of migraine depends on anxious depression; - (3) whether the association between migraine and anxious depression is causal. BACKGROUND Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association. METHODS A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method. RESULTS Modest but significant phenotypic (rP=0.28), genetic (rG=0.30), and nonshared environmental (rE=0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship. CONCLUSIONS These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands

CONTEXT People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders. OBJECTIVES To undertake a comprehensive genome-wide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency. DESIGN Genome-wide linkage scan. SETTING Twin individuals and their family members from Australia and the Netherlands. PARTICIPANTS Nineteen thousand six hundred thirty-five sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers. METHODS Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results. RESULTS Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice. CONCLUSIONS Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.

Using old concepts to gain new insights: Addressing the issue of consistency

Purpose – This paper aims to go beyond a bookkeeping approach to evolutionary analysis whereby surviving firms are better adapted and extinct firms were less adapted. From discussion of the preliminary findings of research into the Hobart pizza industry, evidence is presented of the need to adopt a more traditional approach to applying evolutionary theories with organizational research. Design/methodology/approach – After a brief review of the relevant literature, the preliminary findings of research into the Hobart pizza industry are presented. Then, several evolutionary concepts that are commonplace in ecological research are introduced to help explain the emergent findings. The paper concludes with consideration given to advancing a more consistent approach to employing evolutionary theories within organizational research. Findings – The paper finds that the process of selection cannot be assumed to occur evenly across time and/or space. Within geographically small markets different forms of selection operate in different ways and degrees requiring the use of more traditional evolutionary theories to highlight the causal process associated with population change. Research limitations/implications – The paper concludes by highlighting Geoffrey Hodgson’s Principle of Consistency. It is demonstrated that a failure to truly understand how and why theory is used in one domain will likely result in its misuse in another domain. That, at present, too few evolutionary concepts are employed in organisational research to ensure an appreciation of any underlying causal processes through which social change occurs. Originality/value – The concepts introduced throughout this paper, whilst not new, provide new entry points for organizational researchers intent on employing an evolutionary approach to understand the process of social change.

The long-run impact of Information and Communication Technology on economic output: The case of Australia

This paper investigates the cointegration and causal relationships between Information and Communication Technology (ICT) and economic output in Australia using data for about five decades. The framework used in this paper is the single-sector aggregate production function, which is the first comprehensive approach of this kind to include ICT and non-ICT capital and other factors to examine long-run Granger causality. The empirical evidence points to a cointegration relationship between ICT capital and output, and implies that ICT capital Granger causes economic output and multifactor productivity, as does non-ICT capital.

A reassessment of energy and GDP relationship: The case of Australia

This paper investigates the long- and short-run relationships between energy consumption and economic growth in Australia using the bound testing and the ARDL approach. The analytical framework utilized in this paper includes both production and demand side models and a unified model comprising both production and demand side variables. The energy-GDP relationships are investigated at aggregate as well as several disaggregated energy categories, such as coal, oil, gas and electricity. The possibilities of one or more structural break(s) in the data series are examined by applying the recent advances in techniques. We find that the results of the cointegration tests could be affected by the structural break(s) in the data. It is, therefore, crucial to incorporate the information on structural break(s) in the subsequent modelling and inferences. Moreover, neither the production side nor the demand side framework alone can provide sufficient information to draw an ultimate conclusion on the cointegration and causal direction between energy and output. When alternative frameworks and structural break(s) in time series are explored properly, strong evidence of a bidirectional relationship between energy and output can be observed. The finding is true at both the aggregate and the disaggregate levels of energy consumption.

The dopamine-mediation of perception hypothesis and the implications for schizophrenia

- Background Following Kapur’s hypothesis [1] that schizophrenia is the intensification of phenomenological experience caused by the upregulation of dopamine, a survey of observed dopamine responses to phenomenal information was conducted. - Method An integrative study. - Results When considered in the light of the ecological theory of perception (ETP) [2] and global workspace theory (GBT) [3] Kapur’s hypothesis makes sense: Both the ETP and the GBT require an agent to attribute salience to perceptual information in order to filter an infinite array of available information and usefully sort information by importance. Dopamine may be the primary agent for this purpose. Thus perception itself is suspected as being a dopamine-mediated, and the symptoms and signs of schizophrenia may therefore be the result of dopamine dysfunction. - Conclusions The application of both ETP and GBT to the dopamine hypothesis gives the hypothesis a much-needed causal mechanism and the confl uence of these theories also provides ETP with a neurological perceptual fi lter. This paper provides a compelling model for schizophrenia; a hypothesis that ties perceptual theory to Kapur ’ s concept of dopamine-mediated salience.

A study of professional advisers in Australia

Since 2002, ACPNS has been surveying professional advisers to affluent Australians intermittently to seek their views and experiences around client and personal philanthropy. Why?: because professional advisers on finance, wealth management, law, accounting, taxation, estate management and beyond are an important nexus with people who have the capacity to channel significant funding into community need. Overall, this study suggests a slight shift away from advising affluent clients on philanthropic matters. It also highlights some perceived lack of organisational and professional association support and the feeling of many advisers that they do not have the expertise yet to advise in this area. These results provide thought fodder for advisers, their organisations and sector bodies.

An online community designed to support future makers in educational reform

Australian education is undergoing national reform at many levels. The school sector, where preservice teachers will be employed, are adjusting to the demands of the National Curriculum and improving teacher quality through the National Professional Standards for Teachers. In addition, the university sector, where pre-service teachers are prepared, is undergoing its own education reform through the introduction of a demand-driven system and ensuring quality for tertiary education interns through the Higher Education Standards Framework. In moving to prepare preservice teachers for the school system; universities are grappling with the double-barreled approach to teacher quality; quality within the university course and quality within the student teachers being prepared. Through a collaborative partnership including university lecturers, Department of Education central administration staff, school principals, school coordinators, practicum supervisors, mentor teachers and pre-service teachers; the stakeholders have formed an online community of learners engaging in reflective practice who are committed to improving teacher quality. This online community not only links the key stakeholders within the project, it facilitates the nexus between theory and practice often missing in our pre-service teacher placements. This paper reports preliminary data about an initiative to ensure final year pre-service teachers are aspiring to meet the graduate professional standards through the use of an innovative online community.

Unbounding the interaction design problem: The contribution of HCI in three interventions for well-being

In this paper we consider HCI's role in technology interventions for health and well-being. Three projects carried out by the authors are analysed by appropriating the idea of a value chain to chart a causal history from proximal effects generated in early episodes of design through to distal health and well-being outcomes. Responding to recent arguments that favour bounding HCI's contribution to local patterns of use, we propose an unbounded view of HCI that addresses an extended value chain of influence. We discuss a view of HCI methods as mobilising this value chain perspective in multi-disciplinary collaborations through its emphasis on early prototyping and naturalistic studies of use.

Psychosocial presentation of revisional LAGB patients: A qualitative study

This qualitative study offers insight into the experiences, expectations, perceptions and beliefs that may lead to laparoscopic adjustable gastric band patients’ failure to achieve expected weight loss and seek revisional bariatric surgery. The 23 participants from two sites were interviewed and data were analysed from a grounded theory methodology in order to build a causal model. Analysis of participants’ reports identified ‘unrealistic expectations of the LAGB’ as the core category. Additionally, the restriction of the band had a negative impact on participants’ social interactions, leading to feelings of deprivation and, thus, to a desire for reward from food choices and consequently an increase of consumption of high-calorie-dense foods. These foods were chosen because of their specific texture or ability to provide reward. The resulting increase in weight or failure to achieve excess weight loss, led to feelings of shame and loneliness and emotional eating resulting in increased the consumption of rewarding foods. Thus, identifying unrealistic expectations of laparoscopic adjustable gastric band (LAGB) and emotional eating behaviours are important in those who are present initially for primary bariatric and revisional bariatric surgery, as they may contribute specifically to these patients’ weight regain and consequent failure to achieve excess weight loss.

A relational approach to direct mail consumption

- Purpose This paper aims to investigate how direct mail consumption contributes to brand relationship quality. Store flyers and other direct mailings continue to play a significant role in many companies’ communication strategies. Research on this topic predominantly investigates driving store traffic and sales. Less is known regarding the consumer side, such as the value that consumers may derive from the consumption of direct mailings and the effects of such a value on brand relationship quality. To address this limitation, this paper tests a causal model of the contribution of direct mail value to brand commitment, drawing on a value framework that integrates social theory of engagement regimes and literature on experiential customer value. - Design/methodology/approach The empirical work of this paper is based on a rigorous four-study mixed methods design, involving qualitative study, confirmatory factor analysis and partial least squares structural modeling. - Findings The authors develop two second-order formatively designed scales – familiar value and planned value scales – that illustrate the role of engagement regimes in consumer behavior. Although both types of value contribute equally to direct mail attachment, they exert contrasting effects on other mediational consumer responses, such as reading and gratitude. Finally, the proposed theoretical model appears to be robust in predicting customers’ brand commitment. - Research limitations/implications This study provides new insights into the research on consumer value and brand relational communication. - Originality/value This study is the first to consider consumer benefits from the social perspective of engagement regimes.

Human error risk management methodology for rail crack incidents

The paper presents an innovative approach to modelling the causal relationships of human errors in rail crack incidents (RCI) from a managerial perspective. A Bayesian belief network is developed to model RCI by considering the human errors of designers, manufactures, operators and maintainers (DMOM) and the causal relationships involved. A set of dependent variables whose combinations express the relevant functions performed by each DMOM participant is used to model the causal relationships. A total of 14 RCI on Hong Kong’s mass transit railway (MTR) from 2008 to 2011 are used to illustrate the application of the model. Bayesian inference is used to conduct an importance analysis to assess the impact of the participants’ errors. Sensitivity analysis is then employed to gauge the effect the increased probability of occurrence of human errors on RCI. Finally, strategies for human error identification and mitigation of RCI are proposed. The identification of ability of maintainer in the case study as the most important factor influencing the probability of RCI implies the priority need to strengthen the maintenance management of the MTR system and that improving the inspection ability of the maintainer is likely to be an effective strategy for RCI risk mitigation.

Predictive technology and natural hazards: Risk for Australian planning authorities?

Purpose The object of this paper is to examine whether the improvements in technology that enhance community understanding of the frequency and severity of natural hazards also increased the risk of potential liability of planning authorities in negligence. In Australia, the National Strategy imposes a resilience based approach to disaster management and stresses that responsible land use planning can reduce or prevent the impact of natural hazards upon communities. Design/methodology/approach This paper analyses how the principles of negligence allocate responsibility for loss suffered by a landowner in a hazard prone area between the landowner and local government. Findings The analysis in this paper concludes that despite being able to establish a causal link between the loss suffered by a landowner and the approval of a local authority to build in a hazard prone area, it would be in the rarest of circumstances a negligence action may be proven. Research limitations/implications The focus of this paper is on planning policies and land development, not on the negligent provision of advice or information by the local authority. Practical implications This paper identifies the issues a landowner may face when seeking compensation from a local authority for loss suffered due to the occurrence of a natural hazard known or predicted to be possible in the area. Originality/value The paper establishes that as risk managers, local authorities must place reliance upon scientific modelling and predictive technology when determining planning processes in order to fulfil their responsibilities under the National Strategy and to limit any possible liability in negligence.