Constraints on Compact Binary Formation and Effective Gravitational Wave Likelihood Approximation

Since the initial discovery of gravitational-waves from merging black holes, the LIGO Scientific Collaboration together with Virgo and KAGRA have published 90 gravitational-wave observations of compact binary mergers in the Gravitational-Wave Transient Catalog papers. One of the quintessential questions of this decade in gravitational-wave astronomy is the characterization and impact of the population of observed gravitational-wave signals from merging black holes and neutron stars. Now, there is greater incentive than ever to study the formation channels for these compact binary mergers. In this work, we carry out an investigation of isolated binary evolution formation channel, comparing predictions of the gravitational-wave population from the StarTrack synthetic universe simulations to the observed population of compact binary mergers in order to constrain certain astrophysical processes in binary evolution. In due course, we construct, apply, and provide parametric and non-parametric models for the likelihood function of the full set of astrophysical parameters of each event in the Gravitational-Wave Transient Catalogs, including truncated multivariate normal distributions normalized on a bounded interval, which we have shared in our associated publications [63, 64]. We present the findings of our investigation of the formation parameters for the isolated binary evolution formation channel for compact objects. We have uncovered confounding systematic effects in our model by considering the agreement and disagreement of predictions based on the event rate and mass distribution. Furthermore, our preliminary results demonstrate the benefits of a multi-dimensional analysis which is sensitive to the interdependence of the predicted detection population on many formation parameters. Our essential contribution is therefore a method for carrying out such an analysis efficiently, while considering its self-consistency. We discuss potential sources of bias as we also present the properties of our best binary evolution models, which are consistent with unrestricted stellar mass loss due to winds, high mass and angular momentum loss to ejected portions of a common envelope, and substantial black hole supernova recoil kicks. We conclude with a discussion of the impact of these activities for gravitational-wave and multi-messenger astronomy

Dating violence: Women who broke it off permanently

Dating violence is defined as a dyadic interaction involving the perpetration or threat of a violence, which, to include psychological violence prevents the victim from leaving the abusive relationship. However, some women can break it off and keep off permanently. This research aims to analyze the social representations and perspectives of young women who were victims of dating violence and ended their relationship by their own initiative, permanently.info:eu-repo/semantics/publishedVersio

Sexual Violence against Children and Adolescents: A Developmental Victimology

In recent decades, there has been an increase in the number of studies on sexual violence against children and adolescents, however, this was the last form of abuse to be studied. This article presents some results from these studies, in particular, concepts, epidemiology, and consequences. We also propose a reflection on the confusion between sexual assault and pedophilia, concluding that there is a consensus among the scientific community that not all sexual perpetrators of children and adolescents are pedophiles and not all pedophiles are sexual perpetrators.info:eu-repo/semantics/publishedVersio

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.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 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). 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.Peer reviewe

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression

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

Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen.Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.Peer reviewe

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants with Treatment Resistance in Schizophrenia

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10501) and individuals with non-TRS (n = 20325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85490 participants (48635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P =.001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P =.04). Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance

Nuevos datos sobre Carodnia feruglioi (Carodniidae, Xenungulata) del Eoceno temprano de Patagonia (Argentina).

The species Carodnia feruglioi and ‘Ctalecarodnia cabrerai’ (Xenungulata) were originally described on scarce fragments of teeth from the current Peñas Coloradas Formation at Bajo Palangana (Chubut Province, Argentina). Based on them, the ‘Carodnia horizon’ was named containing one of the oldest native ungulates from South America. However, the type material of these enigmatic xenungulates has remained unknown for more than 80 years, and no updates were performed since their original descriptions. Here, the identification and re-study of the type material, as well as other unpublished specimens from several collections, allowed us to reconstruct part of the dentition of Carodnia feruglioi, describe previously-unknown teeth (e.g., incisors, lower canine, first and second lower molars, and upper molars) and introduce new dental characters for this species. Using length and width ratios of lower dentition (fourth lower premolar, second and third lower molars) as proxies, we compared the metric disparity among the Carodnia species. Based on this study, we provide an emended diagnosis for both the genus and species Carodnia feruglioi and establish comparisons among the six xenungulate documented.Las especies Carodnia feruglioi and ‘Ctalecarodnia cabrerai’(Xenungulata) fueron descritas originalmente a partir de escasos fragmentos de dientes procedentes de la actual Formación Peñas Coloradas en Bajo Palangana (Provincia de Chubut, Argentina). Estas especies fueron la base para definir el denominado ‘horizonte Carodnia’ que incluye uno de los ungulados nativos más antiguos conocidos de América del Sur. Sin embargo, el material tipo de estos xenungulados enigmáticos ha permanecido desconocido por más de 80 años y no se realizaron actualizaciones desde sus descripciones originales. En este trabajo, se identifica y reestudia el material tipo, así como también otros especímenes inéditos de distintas colecciones, lo que nos permitió reconstruir parte de la dentición de Carodnia feruglioi, describir algunos dientes previamente desconocidos (e.g., incisos, canino inferior, primer y segundo molares inferiores, y molares superiores) y dar conocer nuevos caracteres dentales para la especie. Utilizando las relaciones entre el largo y ancho de los dientes inferiores (cuarto premolar inferior, segundo y tercer molares inferiores) como indicadores, comparamos la disparidad métrica entre las especies de Carodnia. A partir de este estudio, proporcionamos una diagnosis emendada para el género y especie Carodnia feruglioi y establecemos comparaciones entre las seis especies descritas de Xenungulata.Fil: Vera, Bárbara Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Fornasiero, Mariagabriella. Università di Padova; ItaliaFil: Del Favero, Letizia. Università di Padova; Itali