Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample

A recent genome-wide association study reported association between schizophrenia and the ZNF804A gene on chromosome 2q32.1. We attempted to replicate these findings in our Irish Case-Control Study of Schizophrenia (ICCSS) sample (N=1021 cases, 626 controls). Following consultation with the original investigators, we genotyped three of the most promising single-nucleotide polymorphisms (SNPs) from the Cardiff study. We replicate association with rs1344706 (trend test one-tailed P=0.0113 with the previously associated A allele) in ZNF804A. We detect no evidence of association with rs6490121 in NOS1 (one-tailed P=0.21), and only a trend with rs9922369 in RGRIP1L (one-tailed P=0.0515). On the basis of these results, we completed genotyping of 11 additional linkage disequilibrium-tagging SNPs in ZNF804A. Of 12 SNPs genotyped, 11 pass quality control criteria and 4 are nominally associated, with our most significant evidence of association at rs7597593 (P=0.0013) followed by rs1344706. We observe no evidence of differential association in ZNF804A on the basis of family history or sex of case. The associated SNP rs1344706 lies in approximately 30 bp of conserved mammalian sequence, and the associated A allele is predicted to maintain binding sites for the brain-expressed transcription factors MYT1l and POU3F1/OCT-6. In controls, expression is significantly increased from the A allele of rs1344706 compared with the C allele. Expression is increased in schizophrenic cases compared with controls, but this difference does not achieve statistical significance. This study replicates the original reported association of ZNF804A with schizophrenia and suggests that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.

From Francis Hutcheson to James McCosh: Irish Presbyterians and Defining the Scottish Philosophy in the Nineteenth Century

This article examines the disputes amongst Irish Presbyterians about the teaching of moral philosophy by Professor John Ferrie in the college department of the Royal Belfast Academical Institution in the early nineteenth century and the substantive philosophical and theological issues that were raised. These issues have largely been ignored by Irish historians, but a discussion of them is of general relevance to historians of ideas as they illuminate a series of broader questions about the definition and development of Scottish philosophy. These are represented in the move from two philosophers who had strong connections with Irish Presbyterianism—Francis Hutcheson, the early eighteenth-century moral sense philosopher and theological moderate from County Down, and James McCosh, nineteenth-century exponent of modified Common Sense philosophy at Queen's College Belfast and a committed evangelical. In particular, this article addresses three important themes—the definition and character of ‘the Scottish philosophy’, the relationship between evangelicalism and Common Sense philosophy, and the process of development and adaptation that occurred in eighteenth-century Scottish thought during the first half of the nineteenth century.

The Complexity of Approximately Solving Influence Diagrams

Influence diagrams allow for intuitive and yet precise description of complex situations involving decision making under uncertainty. Unfortunately, most of the problems described by influence diagrams are hard to solve. In this paper we discuss the complexity of approximately solving influence diagrams. We do not assume no-forgetting or regularity, which makes the class of problems we address very broad. Remarkably, we show that when both the treewidth and the cardinality of the variables are bounded the problem admits a fully polynomial-time approximation scheme.

Early-type stars observed in the ESO UVES Paranal Observatory Project - V. Time-variable interstellar absorption

The structure and properties of the diffuse interstellar medium (ISM) on small scales, sub-au to 1 pc, are poorly understood. We compare interstellar absorption-lines, observed towards a selection of O- and B-type stars at two or more epochs, to search for variations over time caused by the transverse motion of each star combined with changes in the structure in the foreground ISM. Two sets of data were used: 83 VLT- UVES spectra with approximately 6 yr between epochs and 21 McDonald observatory 2.7m telescope echelle spectra with 6 - 20 yr between epochs, over a range of scales from 0 - 360 au. The interstellar absorption-lines observed at the two epochs were subtracted and searched for any residuals due to changes in the foreground ISM. Of the 104 sightlines investigated with typically five or more components in Na I D, possible temporal variation was identified in five UVES spectra (six components), in Ca II, Ca I and/or Na I absorption-lines. The variations detected range from 7\% to a factor of 3.6 in column density. No variation was found in any other interstellar species. Most sightlines show no variation, with 3{\sigma} upper limits to changes of the order 0.1 - 0.3 dex in Ca II and Na I. These variations observed imply that fine-scale structure is present in the ISM, but at the resolution available in this study, is not very common at visible wavelengths. A determination of the electron densities and lower limits to the total number density of a sample of the sightlines implies that there is no striking difference between these parameters in sightlines with, and sightlines without, varying components.