Eric T. Meyer

Genomewide Linkage Analyses of Bipolar Disorder: A New Sample of 250 Pedigrees from the National Institute of Mental Health Genetics Initiative

We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.

Family-based association of FKBP5 in bipolar disorder.

The FKBP5 gene product forms part of a complex with the glucocorticoid receptor and can modulate cortisol-binding affinity. Variations in the gene have been associated with increased recurrence of depression and with rapid response to antidepressant treatment. We sought to determine whether common FKBP5 variants confer risk for bipolar disorder. We genotyped seven tag single-nucleotide polymorphisms (SNPs) in FKBP5, plus two SNPs previously associated with illness, in 317 families with 554 bipolar offspring, derived primarily from two studies. Single marker and haplotypic analyses were carried out with FBAT and EATDT employing the standard bipolar phenotype. Association analyses were also conducted using 11 disease-related variables as covariates. Under an additive genetic model, rs4713902 showed significant overtransmission of the major allele (P=0.0001), which was consistent across the two sample sets (P=0.004 and 0.006). rs7757037 showed evidence of association that was strongest under the dominant model (P=0.001). This result was consistent across the two datasets (P=0.017 and 0.019). The dominant model yielded modest evidence for association (P<0.05) for three additional markers. Covariate-based analyses suggested that genetic variation within FKBP5 may influence attempted suicide and number of depressive episodes in bipolar subjects. Our results are consistent with the well-established relationship between the hypothalamic–pituitary–adrenal (HPA) axis, which mediates the stress response through regulation of cortisol, and mood disorders. Ongoing whole-genome association studies in bipolar disorder and major depression should further clarify the role of FKBP5 and other HPA genes in these illnesses.

Genome-wide scan and conditional analysis in bipolar disorder: Evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees

BACKGROUND In 1989 the National Institute of Mental Health began a collaborative effort to identify genes for bipolar disorder. The first 97 pedigrees showed evidence of linkage to chromosomes 1, 6, 7, 10, 16, and 22 (Nurnberger et al 1997). An additional 56 bipolar families have been genotyped, and the combined sample of 153 pedigrees studied. METHODS Three hierarchical affection status models were analyzed with 513 simple sequence repeat markers; 298 were common across all pedigrees. The primary analysis was a nonparametric genome-wide scan. We performed conditional analyses based on epistasis or heterogeneity for five regions. RESULTS One region, on 16p13, was significant at the genome-wide p <.05 level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12) showed nominally significant linkage findings (p </=.01). Conditional analysis assuming epistasis identified a significant increase in linkage at four regions. Families linked to 6q24 showed a significant increase in nonparametric logarithms of the odds (NPL) scores at 5q11 and 7q21. Epistasis also was observed between 20p12 and 13q21, and 16p13 and 9q21. CONCLUSIONS The findings are presented in rank order of nominal significance. Several of these regions have been previously implicated in independent studies of either bipolar disorder or schizophrenia. The strongest finding is at 16p13 at D16S748 with an NPL of 3.3, there is evidence of epistasis between this locus and 9q21. Application of conditional analyses is potentially useful in larger sample collections to identify susceptibility genes of modest influence that may not be identified in a genome-wide scan aimed to identify single gene effects.

Evidence of association between brain-derived neurotrophic factor gene and bipolar disorder

Objective Brain-derived neurotrophic factor (BDNF) plays an important role in the survival, differentiation, and outgrowth of select peripheral and central neurons throughout adulthood. Growing evidence suggests that BDNF is involved in the pathophysiology of mood disorders. Methods Ten single nucleotide polymorphisms (SNPs) across the BDNF gene were genotyped in a sample of 1749 Caucasian Americans from 250 multiplex bipolar families. Family-based association analysis was used with three hierarchical bipolar disorder models to test for an association between SNPs in BDNF and the risk of bipolar disorder. In addition, an exploratory analysis was performed to test for an association of the SNPs in BDNF and the phenotypes of rapid cycling and episode frequency. Results Evidence of association (P<0.05) was found with several of the SNPs using multiple models of bipolar disorder; one of these SNPs also showed evidence of association (P<0.05) with rapid cycling. Conclusion These results provide further evidence that variation in BDNF affects the risk for bipolar disorder.

Emerging practices and perspectives on Big Data analysis in economics: Bigger and better or more of the same?

Although the terminology of Big Data has so far gained little traction in economics, the availability of unprecedentedly rich datasets and the need for new approaches – both epistemological and computational – to deal with them is an emerging issue for the discipline. Using interviews conducted with a cross-section of economists, this paper examines perspectives on Big Data across the discipline, the new types of data being used by researchers on economic issues, and the range of responses to this opportunity amongst economists. First, we outline the areas in which it is being used, including the prediction and ‘nowcasting’ of economic trends; mapping and predicting influence in the context of marketing; and acting as a cheaper or more accurate substitute for existing types of data such as censuses or labour market data. We then analyse the broader current and potential contributions of Big Data to economics, such as the ways in which econometric methodology is being used to shed light on questions beyond economics, how Big Data is improving or changing economic models, and the kinds of collaborations arising around Big Data between economists and other disciplines.

Socio-Technical Interaction Networks: A Discussion of the Strengths, Weaknesses and Future of Kling's STIN Model

The Socio-Technical Interaction Network (STIN) strategy for social informatics research was published late in Rob Kling’s life, and as a result, he did not have time to pursue its continued development. This paper aims to summarize existing work on STINs, identify key themes, strengths, weaknesses and limitations, and to suggest trajectories for the future of STIN research. The STIN strategy for research on socio-technical systems offers the potential for useful insights into the highly intertwined nature of social factors and technological systems, however a number of areas of the strategy remain underdeveloped and offer the potential for future refinement and modification.

Reinventing Research? Information Practices in the Humanities.

Researchers in the humanities adopt a wide variety of approaches to their research. Their work tends to focus on texts and images, but they use and also create a wide range of information resources, in print, manuscript and digital forms. Like other researchers, they face multiple demands on their time, and so they find the ease and speed of access to digital resources very attractive: some of them note that they are reluctant on occasion to consult texts that require a trip to a distant library or archive. Nevertheless, none of the participants in our study is yet ready to abandon print and manuscript resources in favour of digital ones. Rather, they engage with a range of resources and technologies, moving seamlessly between them. Such behaviours are likely to persist for some time.This is reflected also in how researchers disseminate their research. The overwhelmingly dominant channels are the long-established ones such as journal articles, conferences and workshops, monographs and book chapters. We found only limited use – except among philosophers - of blogs and other social media. We noted the doubts expressed in other fields about quality assurance for users of such media, but also concerns about how best to present material that will be read by non-academic audiences.A key change in humanities research over the past 10-15 years has been the growth of more formal and systematic collaboration between researchers. This is a response in part to new funding opportunities, but also to the possibilities opened up by new technology. Over recent years there has also been a shift from the model under which technology specialists tell researchers how to do their research to more constructive engagement. Like other researchers, scholars in the humanities use what works for them, finding technologies and resources that fit their research, and resisting any pressure to use something just because it is new.But there is little evidence as yet of their taking full advantage of the possibilities of more advanced tools for text-mining, grid or cloud computing, or the semantic web; and only limited uptake of even simple, freely-available tools for data management and sharing. Rather, they manage and store information on their desktops and laptops, and share it with others via email. Barriers to the adoption and take up of new technologies and services include lack of awareness and of institutional training and support, but also lack of standardization and inconsistencies in quality and functionality across different resources. These make for delays in research, repetitive searching, and limitations on researchers’ ability to draw connections and relationships between different resources.

Untangling the Web of E-Research: Towards a Sociology of Online Knowledge

e-Research is a rapidly growing research area, both in terms of publications and in terms of funding. In this article we argue that it is necessary to reconceptualize the ways in which we seek to measure and understand e-Research by developing a sociology of knowledge based on our understanding of how science has been transformed historically and shifted into online forms. Next, we report data which allows the examination of e-Research through a variety of traces in order to begin to understand how knowledge in the realm of e-Research has been and is being constructed. These data indicate that e-Research has had a variable impact in different fields of research. We argue that only an overall account of the scale and scope of e-Research within and between different fields makes it possible to identify the organizational coherence and diffuseness of e-Research in terms of its socio-technical networks, and thus to identify the contributions of e-Research to various research fronts in the online production of knowledge.

Creation and Control in the Photographic Process: iPhones and the Emerging Fifth Moment of Photography

This article underlines some aspects that relate, on the one side, to the technological devices necessary to photography production and, on the other, the kind of practices that shape and are shaped by those devices. It discusses how those relationships have shaped different visual regimes. Based on theoretical approaches like Science and Technology Studies (STS) and the Socio-technical Interactions Network (STIN) perspective, the article starts with a brief historical description focusing on the production of photos as a three-step process: 1) infrastructural elements of image production; 2) technologies of processing images; and 3) distribution/showing of images. It is proposed that photography has had four moments in this history. Finally, the article discusses the latest socio-technological practices, and proposes that the iPhone is the best example of the kind of devices that are possibly opening a fifth moment in photography technologies.

The World Wide Web of Research and Access to Knowledge

This paper examines the shift to online knowledge in research. In recent years there has been a major transformation in how formal and informal science communication is disseminated by electronic means. At the same time, researchers’ practices in accessing knowledge and information have changed, particularly in the use of search engines and digitized resources apart from traditional journals. While we still know little about how this affects the nature of research, particularly in light of disciplinary differences, we reject here the idea that the simple growth of outputs and proliferation of outputs also leads straightforwardly to a richer and more diverse information and knowledge environment. Instead, we argue that gatekeepers such as search engines which shape online visibility, combined with competition for limited attention space at the leading edge of research, leads to a different model of how access to knowledge and information is being shaped.