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)

Insects as sustainable feed ingredients: Case study: Assessing the performance of broilers fed on diets containing crude and processed housefly larval meal

Musca domestica larvae reared on poultry manure and used as a meal or “fat-washed” extract have been assessed for their suitability as a partial replacement for soybean meal and oil in a broiler performance trial. This trial formed a component of a larger European Union funded research programme that investigated the potential for the exploitation insects as a protein source for animal feed. Insect meal comprised approx. 42 % protein and 29 % fat on a dry wt. basis, whereas processed (fat-washed) extract contained 68 % protein and 13 % fat. Insect protein contained higher levels of key amino acids lysine, threonine, methionine, cysteine and tryptophan but a lower level of arginine as compared to soybean meal. Insect fat was comprised principally of saturated palmitic and monounsaturated palmitoleic and oleic fatty acids with notably lower levels of polyunsaturated linolenic and linoleic fatty acids as compared to soya bean oil. Inclusion of crude or processed insect meals at 2 % and 1.25 % respectively, had no significant positive or detrimental effects on broiler health or performance. All treatments showed highly similar gains in body weight, and food conversion ratio’s (FCR’s) over a 39-day trial period. No taints were detected in meat derived from insect fed animals. Nutritional analysis of meat derived from the trial showed that protein, amino acid and trace element levels were comparable between treatments. Total fat content was higher in meat derived from birds fed on full-fat insect meal as compared to fat-washed diets or control treatments. A comprehensive safety screen showed contaminant levels in the insect meal to be either undetectable or below recommended maximum concentrations for feed (WHO, Codex, EC) and levels in meat were comparable between insect and control treatments

Social cognition and quality of life in schizophrenia

Schizophrenia is associated with poor quality of life (QOL). Whereas the effects of neurocognitive deficits and psychopathology on QOL of schizophrenia patients have recently been elucidated, little is known about social cognitive deficits in this regard. This study investigated the influence of social cognition on QOL in schizophrenia. A sample of 1032 patients, 1011 of their siblings, and 552 healthy controls was recruited from the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. Participants completed a battery of cognitive tests, including social cognitive tests on theory of mind and emotion perception. To assess QOL the World Health Organization QOL Assessment-BREF (WHOQOL-BREF) was used. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Social cognitive performance was significantly worse in patients compared to siblings and healthy controls. Patients had the poorest QOL, while QOL in healthy controls was better than in siblings. Theory of mind but not emotion perception or neurocognition was associated with QOL in patients, whereas neurocognition was the only significant predictor of QOL in siblings and healthy controls. There was a significant interaction between theory of mind and symptom severity with respect to QOL. Our study indicates that social cognition is associated with QOL in schizophrenia. Theory of mind rather than emotion perception is associated with QOL, and this association is moderated by schizophrenia symptoms. In particular, patients with relatively unimpaired theory of mind and more severe schizophrenia symptoms have poor QOL and could therefore benefit from therapeutic intervention. © 2012 Elsevier B.V

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies