Association between oxytocin receptor gene polymorphisms and self-rated 'empathic concern' in schizophrenia

The nonapeptide oxytocin (OXT) and its receptor (OXTR) have been implicated in social cognition, empathy, emotion and stress regulation in humans. Previous studies reported associations between OXT and OXTR genetic polymorphisms and risk for disorders characterized by impaired socio-emotional functioning, such as schizophrenia and autism. Here we investigate the influence of two single nucleotide polymorphisms (SNPs) within the OXTR gene on a measure of socio-emotional functioning in schizophrenic patients. OXTR SNPs that were previously investigated in other studies were genotyped in 145 patients diagnosed with schizophrenia according to DSM-IV and 145 healthy controls matched for age and gender. The Interpersonal Reactivity Index (IRI) was used to assess cognitive ('perspective taking'), affective ('empathic concern') and self-related ('personal distress') dimensions of empathy. No group differences in genotype frequencies were observed. MANCOVA revealed a significant main (F [1,282] = 10.464; pGG) with 'empathic concern'. Within the schizophrenia group, linear regression analysis determined OXTR rs2254298 genotype, PANSS negative and general symptom score, and age of disease onset as being significantly associated with 'empathic concern'. OXTR rs2254298 significantly impacted PANSS general psychopathology scores. No associations were found for OXTR rs53576, IRI 'perspective taking' or 'personal distress' ratings. Our preliminary findings support hypotheses about an involvement of OXTR rs2254298 in emotional empathy in schizophrenic and healthy individuals, warranting independent replication

Dietary fiber and its role in performance, welfare, and health of pigs

Dietary fiber (DF) is receiving increasing attention, and its importance in pig nutrition is now acknowledged. Although DF for pigs was frowned upon for a long time because of reductions in energy intake and digestibility of other nutrients, it has become clear that feeding DF to pigs can affect their well-being and health. This review aims to summarize the state of knowledge of studies on DF in pigs, with an emphasis on the underlying mode of action, by considering research using DF in sows as well as suckling and weaned piglets, and fattening pigs. These studies indicate that DF can benefit the digestive tracts and the health of pigs, if certain conditions or restrictions are considered, such as concentration in the feed and fermentability. Besides the chemical composition and the impact on energy and nutrient digestibility, it is also necessary to evaluate the possible physical and physiologic effects on intestinal function and intestinal microbiota, to better understand the relation of DF to animal health and welfare. Future research should be designed to provide a better mechanistic understanding of the physiologic effects of DF in pigs

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations:Experience from the MJFF Global Genetic Parkinson's Disease Project

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.</p

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.[Background] As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited.[Objective] The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.[Methods] We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.[Results] We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.[Conclusions] Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.This project was funded by The Michael J. Fox Foundation (ID 15015.02)Peer reviewe

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Empathy and oxytocin and oxytocin receptor gene polymorphisms in patients with schizophrenia

Einleitung: Beeinträchtigungen empathischer Fähigkeiten stellen ein wichtiges klinisches Merkmal der Schizophrenie dar und beeinflussen die funktionelle Prognose der Erkrankung. Emotionale Komponenten der Empathie sind bei Schizophrenie weniger gut erforscht als kognitive. Genetische Polymorphismen des Oxytocin (OXT)- und Oxytocin-Rezeptor (OXTR)- Gens wurden bereits mit Krankheiten, welche von sozialen oder emotionalen Defiziten geprägt sind, sowie mit sozialer Kognition und Empathie bei Gesunden in Verbindung gebracht. In drei Studien sollen Assoziationen verschiedener Einzelnukleotid- Polymorphismen (SNPs) im OXT- und OXTR-Gen mit der Diagnose einer Schizophrenie und der Fähigkeit zur Empathie sowie emotionale und kognitive Empathie und Aspekte der Emotionsverarbeitung im Hinblick auf die psychosoziale Funktion bei Patienten mit Schizophrenie untersucht werden. Methodik: Es erfolgte die Genotypisierung von zwei SNPs im OXT- und fünf SNPs im OXTR- Gen bei schizophrenen Patienten und gesunden Kontrollprobanden. Als behaviorale Parameter für Empathie verwendeten wir den Interpersonal Reactivity Index (IRI) und den Multifaceted Empathy Test (MET). Zur Beurteilung von emotionaler Ansteckung und Emotionsverarbeitung wurden die Subjective Experience of Emotions Scale (SEE) und die Emotional Contagion Scale (ECS) eingesetzt. Ergebnisse: Es ließen sich eine signifikante Assoziation des OXTR SNP rs53576 (A>G) und OXTR SNP rs237885 (T>G) mit der Diagnose einer Schizophrenie und ein signifikanter Einfluss des OXTR SNP rs2254298 auf „empathic concern“ im IRI, als Messparameter emotionaler Empathie, nachweisen. Patienten mit Schizophrenie zeigten Beeinträchtigungen der kognitiven, nicht jedoch der emotionalen Empathie. Sie zeigten mehr Ansteckung mit negativen Gefühlen, vermehrtes Erleben von Emotionsmangel und Emotionsüberflutung, mehr imaginative Symbolisierung von Emotionen und weniger Erleben von Selbstkontrolle im Vergleich zu gesunden Individuen. Die psychosoziale Funktion wurde neben der kognitiven Empathie durch geringeren subjektiven Distress in zwischenmenschlichen Situationen und das vermehrte Erleben von Emotionsüberflutung prädiziert. Schlussfolgerung: Die Ergebnisse sprechen für einen möglichen Einfluss oxytocinerger Gene auf die Vulnerabilität für Schizophrenie und weisen auf eine Assoziation von OXTR-Gen Polymorphismen mit emotionaler Empathie bei Schizophrenie hin. Sie zeigen, dass Aspekte der Emotionsverarbeitung möglicherweise wichtige Einflussfaktoren empathischer Fähigkeiten von schizophrenen Patienten darstellen und verdeutlichen die Wichtigkeit subjektiver Prozesse zum Management negativer Emotionen als Einflussfaktoren für die psychosoziale Prognose.Objectives: Deficits in empathic abilities are an important clinical feature of schizophrenia and predict the functional outcome of the disease. In contrast to cognitive components, affective components of empathy are less well understood. Oxytocin (OXT) and Oxytocin receptor (OXTR) gene polymorphisms have already been associated with diseases marked by socio- emotional deficits as well as social cognition and empathy in healthy individuals. In three studies we investigated an association of different single nucleotide polymorphisms (SNPs) within the OXT and OXTR gene with schizophrenia, their possible influence on empathy in schizophrenia, furthermore affective and cognitive components of empathy in the context of the subjective experience of emotion processing in schizophrenia and their influence on psychosocial function. Methods: Two SNPs within the OXT gene and five SNPs within the OXTR gene were genotyped in schizophrenic patients and healthy controls. We used the Interpersonal Reactivity Index (IRI) and Multifaceted Empathy Test (MET) as empathy measures, the Subjective Experience of Emotion Scale (SEE) and Emotional Contagion Scale (ECS) to assess emotional contagion and aspects of emotion processing. Results: We found a significant association of OXTR SNP rs53576 (A>G) and OXTR SNP rs237885 (T>G) with schizophrenia and a significant influence of OXTR SNP rs2254298 on IRI „empathic concern“, representing affective empathy. Patients showed impaired cognitive but not affective empathy. They reported more negative emotional contagion, more lack of emotions and overwhelming emotions, more symbolization of emotions by imagination and less self-control compared to healthy controls. Psychosocial function was predicted by cognitive empathy, less interpersonal distress and the experience of a higher extent of overwhelming emotions. Conclusions: The results suggest a possible influence of oxytocin system genes on schizophrenia vulnerability and an association of OXTR gene polymorphisms with affective empathy in schizophrenia. They indicate that aspects of emotion processing have an important effect on empathic abilities in schizophrenia and illustrate the importance of subjective processes of managing negative emotions as those predict psychosocial outcome

Genetic Variants of Candidate Genes Influencing Milk Yield, Composition and Somatic Cell Score in German Holstein Cows

The aims of this study were to estimate the genotype and allele frequencies and genotype effects located in the Acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1), Leptin (Lep/ob),Growth hormone receptor (GHR), Prolactin receptor (PRLR), and Kappa casein (CSN3) genes on milk yield, composition and somatic cell score (SCS) in German Holstein cows. The association analyses were based on data from 1380 German Holstein cows. The allele frequencies of the DGAT1 K232A were 44.2% and 55.8% for the Lysine and Alanine variant, respectively. The allele substitution effect for the Lysine variant was significantly increased the fat (0.30%,

Raw data of IRI scores (mean, SD) by OXTR rs2254298 and rs53576 genotypes in schizophrenia patients (SZ, n = 145) and healthy controls (HC, n = 145).

1)<p>T-test for independent samples: T = −3.493, p<0.001.</p