Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Do Personality Traits Modulate the Effect of Emotional Visual Stimuli on Auditory Information Processing?

peer reviewedSeveral lines of evidence attest robust relationships between personality dimensions and emotions, including cognitive aspect of emotion. More particularly, many studies reported strong relationships between extraversion, the behavioral activation system (BAS), and the cognitive processing of positive information, on the one hand, and between neuroticism, the behavioral inhibition system (BIS), and the processing of negative information, on the other hand. Recently, DePascalis, Awari, Matteucci, and Mazzocco (2005) reported that personality traits modulated the effect of the emotional visual stimuli on the mismatch negativity (MMN). The aim of the present study was to replicate these data and extend them to other personality dimensions. Auditory MMN was recorded in normal subjects simultaneously to the presentation of emotional pictures selected as neutral, positive, or negative from the International Affective Picture System, and presented in randomized order. The results support the recent finding that personality (namely, BIS and harm avoidance) modulates the influence of emotional (negative) context on auditory information processing. The present findings suggest that the modulation by personality of change detection in the unattended environment as a function of context valence is limited to unpleasant context

Reference analysis on the use of engineered barriers for isolation of spent nuclear fuel in granite and basalt

This report evaluates the effectiveness of engineered barriers in delaying or reducing the rate of release of radionuclides from spent fuel in geologic respositories in granite and basalt. It was assumed that the major exposure pathway from the respository to humans would be the ground-water system overlying or underlying a site. Hence, this report focuses on ground-water pathways. A geosphere transport model, GETOUT, and the biosphere transport/dose models, ALLDOS and PABLM, were integrated and used to calculate the potential radiological dose that might be received by humans at various times after repository closure