Polygenic risk score analysis of pathologically confirmed Alzheimer's disease

Previous estimates of the utility of polygenic risk score analysis for the prediction of Alzheimer’s disease have given Area Under the Curve estimates of <80%. However, these have been based on the genetic analysis of clinical case control series. Here we apply the same analytic approaches to a pathological case control series and show a predictive AUC of 84%. We suggest that this analysis has clinical utility and that there is limited room for further improvement using genetic data

Jobs for communities: does local economic investment work

New Labour's policies aimed at regenerating poor communities promote economic investment, yet research on how such investment improves employment prospects for local residents over a sustained period is scarce. Using the Darnall area of Sheffield as a case study, this paper considers the degree to which new sectors of employment have been accessed by residents living in the immediate vicinity of a major retail development. Evidence from the 1981, 1991 and 2001 Censuses includes population, employment, migration and travel to work characteristics, which show that many residents remain marginalised from local jobs, raising important issues for contemporary initiatives promoting retail investment as part of a strategy to tackle worklessness

Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Background: There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon. Methods: Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth. Results: Neither genetic measure was associated with season or month of birth within the UKBB sample. Conclusions: As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure

Electron tunnel rates in a donor-silicon single electron transistor hybrid

We investigate a hybrid structure consisting of $20\pm4$ implanted $^{31}$P atoms close to a gate-induced silicon single electron transistor (SiSET). In this configuration, the SiSET is extremely sensitive to the charge state of the nearby centers, turning from the off state to the conducting state when the charge configuration is changed. We present a method to measure fast electron tunnel rates between donors and the SiSET island, using a pulsed voltage scheme and low-bandwidth current detection. The experimental findings are quantitatively discussed using a rate equation model, enabling the extraction of the capture and emission rates.Comment: 10 pages, 3 figure

Borderline personality and attention-deficit hyperactivity traits in childhood are associated with hypomanic features in early adulthood

Background There is limited understanding of the symptomatic development of bipolar disorder from childhood to early adulthood. Aims We assessed whether borderline personality disorder traits, ADHD, and emotional, behavioural and social difficulties during childhood were associated with hypomania assessed in young adulthood. Method We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine associations between measures of childhood psychopathology and lifetime hypomanic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n = 3,372). We also conducted a factor analysis of the HCL to identify latent constructs underlying hypomania, and the extent to which childhood psychopathology was associated with these. Results We identified two factors of the HCL corresponding to energy/mood and risk-taking/irritability. There was evidence of association between childhood borderline personality disorder traits and both hypomania factors, with evidence that the association was stronger with the risk-taking/irritability factor. All individual borderline traits, with the exception of fear of abandonment, were associated with hypomania. There was also evidence of association between most other measures of childhood psychopathology (ADHD, hyperactivity, conduct problems, peer relationship problems and reduced prosocial behaviour) and the risk-taking/irritability factor, but much less consistent evidence of association with the energy/mood factor. Limitations The HCL cannot diagnose bipolar disorder and may be subject to reporting bias. Conclusions A broad range of childhood psychopathologies may represent early markers of risk for hypomania. Further studies are required to understand the mechanisms underlying these associations, and to inform earlier detection of bipolar disorder