Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

FEATURES OF DEVELOPMENT OF SCHOOL PEDAGOGICS HEALTH IN TRANSNISTRIA

The aim of the investigation is to show the features and to define the directions of development of school pedagogics of health in Pridnestrovian Moldavian Republic (PMR). Methods. The methods involve theoretical analysis of sources in the field of pedagogics of health, statistical data, methods of analogy, comparison, correlation, synthesis of information, studying of the best practices of schools of health of PMR. The principles of system and valeological approaches have been involved as the leading methodological reference points. Results and scientific novelty. Intrinsic characteristics and specifics of school pedagogics of health in PMR are disclosed; its genesis during the PostSoviet period is completely presented; the prospects are defined. Positive experience of preservation, strengthening and formation of health of pupils of Pridnestrovian schools is revealed and analysed. Practical significance of research consists that the received results have predictive character and are suitable for design of the organization of a school education system

Implementation of the Model of Noosphere-Aesthetic Education of Primary School Students by Means of Regional Culture

The relevance of the problem of noosphere-aesthetic education of primary school students is due to the need for their entry into noosphere-cultural space of the region which affects the formation of humanistic attitude of students to all life on the earth, their native nature and culture; insufficient theoretical and practical development of the model for the implementation of this phenomenon.The purpose of the article is theoretical substantiation, development and implementation of the model of noosphere-aesthetic education of primary school students by means of regional culture.The leading method of research is modeling which allows to create and implement an integral system of noosphere-aesthetic education of primary school students by means of regional culture.On the basis of cultural and environmental approaches we have defined the content of the concepts "noosphere-aesthetic education of primary school students", “regional culture" and proved the effectiveness of the model for implementing this approach. In this article from the standpoint of cultural and environmental approaches the concept of "noosphere-aesthetic education of primary school students" is clarified, the effectiveness of the implementation model of this phenomenon by means of regional culture is proved, prospects of using its building blocks: target, structural, diagnostic, technological and effective in the education system are substantiated.The results of the research presented in the article and statistical processing of experimental data using R.Fisher's angular coefficient of transformation proved the effectiveness of proposed model in educational process.Practical significance of the study is that diagnostic techniques, program, process unit of the model presented in the article contribute to more efficient noosphere education of primary school students and can be used by teachers of higher school, primary school teachers and educators in their activities

On the Pathomorphological Pattern of the Efficiency of Photodynamic Therapy of Murine Melanoma B16 Using a New Photosensitizer Based on Chlorin e6 Conjugate with a Prostate-Specific Membrane Antigen

Photodynamic therapy (PDT) is an effective treatment for a number of solid malignancies. In this work, the antitumor efficacy of photodynamic therapy for murine B16 melanoma with intravenous administration of a new photosensitizer (PS) based on the chlorin e6 conjugate with a prostate-specific membrane antigen (PSMA) was studied in vivo. We have previously published the data obtained in the first part of the study: the dynamics of PS accumulation in the tumor and surrounding tissues and the antitumor efficacy of the photodynamic therapy, which was evaluated by the regression parameters and morphological characteristics of the tumors—including by the complete regression of the tumors, the absolute growth rate of the tumors among the mice with continued tumor growth, and an increase in life expectancy compared to the control. The criterion for a complete cure was the absence of signs of tumor recurrence within 90 days after therapy. The conducted studies demonstrated the high efficiency of the new photosensitizer for the photodynamic therapy of B16 melanoma. This article presents a continuation of this work, including histological studies of the zones exposed to laser irradiation on the 21st day after treatment and an assessment of the therapeutic potential of photodynamic therapy for the destruction of tumor cells. Pathological studies in the zones of photodynamic exposure revealed that the effectiveness of the PDT depended on the PS dose and the laser irradiation parameters

Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics. 2011; 20:4076–81. [PubMed: 21791550

ABSTRACT Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association (GWA) study and meta-analysis (totalling 7,946 cases and 19,036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10,260 cases and 23,500 controls). In addition to previously-reported alleles in the major histocompatibility complex (MHC) region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) (OR = 1.09, P = 1.9 x 10 -

Common variants at VRK2 and TCF4 conferring risk of schizophrenia

Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10−9] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10−9)