The XO Planetary Survey Project - Astrophysical False Positives

Searches for planetary transits find many astrophysical false positives as a by-product. There are four main types analyzed in the literature: a grazing-incidence eclipsing binary star, an eclipsing binary star with a small radius companion star, a blend of one or more stars with an unrelated eclipsing binary star, and a physical triple star system. We present a list of 69 astrophysical false positives that had been identified as candidates of transiting planets of the on-going XO survey. This list may be useful in order to avoid redundant observation and characterization of these particular candidates independently identified by other wide-field searches for transiting planets. The list may be useful for those modeling the yield of the XO survey and surveys similar to it. Subsequent observations of some of the listed stars may improve mass-radius relations, especially for low-mass stars. From the candidates exhibiting eclipses, we report three new spectroscopic double-line binaries and give mass function estimations for 15 single lined spectroscopic binaries.Comment: 13 pages, 4 figures, accepted to ApJ

Associations Between Schizophrenia Polygenic Liability, Symptom Dimensions, and Cognitive Ability in Schizophrenia

Importance Schizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia. Objective To determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence. Design, Setting, and Participants In a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021. Main Outcomes and Measures Outcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence. Results Of the 1220 study participants, 817 were men (67.0%). Participants’ mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10−4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10−4). Current cognitive ability was associated with genetic liability to schizophrenia (β = −0.11; 95% CI, −0.19 to −0.04; P = 1.63 × 10−3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10−10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = −0.08; 95% CI, −0.14 to −0.02; P = 8.50 × 10−3) but not intelligence PRS. Conclusions and Relevance The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia

Psychosis and the level of mood incongruence in Bipolar Disorder are related to genetic liability for Schizophrenia

Abstract Importance Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms. Objectives To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features. Design Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls. Settings & Participants 4399 BDcases, mean [sd] age-at-interview 46[12] years, of which 2966 were woman (67%) from the BD Research Network (BDRN) were included in the final analyses, with data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland included for comparison. Exposure Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform. Main outcome measure Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS). Results Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)). Conclusion We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms

Leveraging genomic annotations and pleiotropic enrichment for improved replication rates in schizophrenia GWAS

Most of the genetic architecture of schizophrenia (SCZ) has not yet been identified. Here, we apply a novel statistical algorithm called Covariate-Modulated Mixture Modeling (CM3), which incorporates auxiliary information (heterozygosity, total linkage disequilibrium, genomic annotations, pleiotropy) for each single nucleotide polymorphism (SNP) to enable more accurate estimation of replication probabilities, conditional on the observed test statistic (“z-score”) of the SNP. We use a multiple logistic regression on z-scores to combine information from auxiliary information to derive a “relative enrichment score” for each SNP. For each stratum of these relative enrichment scores, we obtain nonparametric estimates of posterior expected test statistics and replication probabilities as a function of discovery z-scores, using a resampling-based approach that repeatedly and randomly partitions meta-analysis sub-studies into training and replication samples. We fit a scale mixture of two Gaussians model to each stratum, obtaining parameter estimates that minimize the sum of squared differences of the scale-mixture model with the stratified nonparametric estimates. We apply this approach to the recent genome-wide association study (GWAS) of SCZ (n = 82,315), obtaining a good fit between the model-based and observed effect sizes and replication probabilities. We observed that SNPs with low enrichment scores replicate with a lower probability than SNPs with high enrichment scores even when both they are genome-wide significant (p < 5x10-8). There were 693 and 219 independent loci with model-based replication rates ≥80% and ≥90%, respectively. Compared to analyses not incorporating relative enrichment scores, CM3 increased out-of-sample yield for SNPs that replicate at a given rate. This demonstrates that replication probabilities can be more accurately estimated using prior enrichment information with CM3

Investigating the genetic architecture of general and specific psychopathology in adolescence

Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age. PRSs for schizophrenia, major depressive disorder, neuroticism and bipolar disorder were generated for individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariate linear regression was used to examine the relationships of these PRSs with psychopathology factors modelled within (i) a correlated factors structure and (ii) a bifactor structure. The schizophrenia PRS was associated with an increase in factors describing psychotic experiences, negative dimension, depression and anxiety, but, when modelling a general psychopathology factor based on these measures, specific effects above this persisted only for the negative dimension. Similar factor relationships were observed for the neuroticism PRS, with a (weak) specific effect only for anxiety once modelling general psychopathology. Psychopathology during adolescence can be described by a general psychopathology construct that captures common variance as well as by specific constructs capturing remaining non-shared variance. Schizophrenia risk genetic variants identified through genome-wide association studies mainly index negative rather than positive symptom psychopathology during adolescence. This has potentially important implications both for research and risk prediction in high-risk samples

Clinical supervision for clinical psychology students in Uganda: an initial qualitative exploration

Background Burn out in clinical psychologists working in low income countries has been reported. Clinical supervisory structures do not yet exist in Uganda. A way to decrease levels of burn out and increase quality of care for people with mental illness is through clinical supervision. The aim of this study was to explore the initial experiences of supervision for clinical psychology students in Uganda to ascertain whether or not clinical supervision is culturally appropriate, and what aspects of supervision had been helpful and unhelpful. Methods A qualitative design with thematic analysis was utilized. A focus group was held with 12 second year clinical psychology students to ask their experiences of receiving supervision. Results Data analysis created five themes. Firstly, the negative emotions that resulted from the training processed were discussed, and how supervision helped and did not help the students to manage these. Secondly, the students voiced that supervision helped them to learn through observational experiences, co-therapist roles and parallel processes within the supervisory relationship. Thirdly, supervision had taught the clinical psychology students their role as a clinical psychology student, how to act within the Ugandan mental health system and skills to conduct therapy. Fourthly, suggestions for the future of supervision were given, with the students requesting for it to start earlier in the training, for supervisors who can meet with the students on a regular basis to be selected and for the training the students receive at university to match the skills required on their placements, with a request for more practical techniques rather than theory. The final theme related to left over miscellaneous data, such as the students agreeing with each other. Conclusions The students stated that supervision was helpful overall, implying that clinical supervision is culturally appropriate for clinical psychology students in Uganda. Suggestions for future supervision were given. In order to decrease high levels of staff burn out in the mental health systems in Uganda, supervisory structures with an emphasis on self care need to be established

Additive genetic variation in schizophrenia risk is shared by populations of African and European descent

Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRβ1 at amino acid position 13, located outside the classical shared epitope (Pomnibus = 6.9 × 10(-135)). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr ≅ Gly > Ser)--but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional Pomnibus = 2.2 × 10(-33)) and 74 (conditional Pomnibus = 1.1 × 10(-8)). Outside of HLA-DRβ1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 × 10(-6)) and HLA-DPβ1 (Phe9, conditional P = 3.0 × 10(-5)) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. HLA-DRB1*09:01) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC

Schizophrenia as a disorder of disconnectivity

Schizophrenia is considered as a neurodevelopmental disorder with genetic and environmental factors playing a role. Animal models show that developmental hippocampal lesions are causing disconnectivity of the prefrontal cortex. Magnetic resonance imaging and postmortem investigations revealed deficits in the temporoprefrontal neuronal circuit. Decreased oligodendrocyte numbers and expression of oligodendrocyte genes and synaptic proteins may contribute to disturbances of micro- and macro-circuitry in the pathophysiology of the disease. Functional connectivity between cortical areas can be investigated with high temporal resolution using transcranial magnetic stimulation (TMS), electroencephalography (EEG), and magnetoencephalography (MEG). In this review, disconnectivity between different cortical areas in schizophrenia patients is described. The specificity and the neurobiological origin of these connectivity deficits and the relation to the symptom complex of schizophrenia and the glutamatergic and GABAergic system are discussed