Genetic Influences Research Articles

Research Review: A review of the past decade offamily and genomic studies on adolescent mentalhealth.

Mental health problems and traits capturing psychopathology are common and often begin during adolescence. Decades of twin studies indicate that genetic factors explain around 50% of individual differences in adolescent psychopathology. In recent years, significant advances, particularly in genomics, have moved this work towards more translational findings. This review provides an overview of the past decade of genetically sensitive studies on adolescent development, covering both family and genomic studies in adolescents aged 10-24 years. We focus on five research themes: (1) co-occurrence or comorbidity between psychopathologies, (2) stability and change over time, (3) intergenerational transmission, (4) gene-environment interplay, and (5) psychological treatment outcomes. First, research shows that much of the co-occurrence of psychopathologies in adolescence is explained by genetic factors, with widespread pleiotropic influences on many traits. Second, stability in psychopathology across adolescence is largely explained by persistent genetic influences, whereas change is explained by emerging genetic and environmental influences. Third, contemporary twin-family studies suggest that different co-occurring genetic and environmental mechanisms may account for the intergenerational transmission of psychopathology, with some differences across psychopathologies. Fourth, genetic influences on adolescent psychopathology are correlated with a wide range of environmental exposures. However, the extent to which genetic factors interact with the environment remains unclear, as findings from both twin and genomic studies are inconsistent. Finally, a few studies suggest that genetic factors may play a role in psychological treatment response, but these findings have not yet been replicated. Genetically sensitive research on adolescent psychopathology has progressed significantly in the past decade, with family and twin findings starting to be replicated at the genomic level. However, important gaps remain in the literature, and we conclude by providing suggestions of research questions that still need to be addressed.

Genome-wide identification, characterization and expression profiles of FORMIN gene family in cotton (Gossypium Raimondii L.)

BackgroundGossypium raimondii serves as a widely used genomic model cotton species. Its genetic influence to enhance fiber quality and ability to adapt to challenging environments both contribute to increasing cotton production. The formins are a large protein family that predominately consists of FH1 and FH2 domains. The presence of the formin domains highly regulates the actin and microtubule filament in the cytoskeleton dynamics confronting various abiotic stresses such as drought, salinity, and cold temperatures.ResultsIn this study, 26 formin genes were analyzed and characterized in G. raimondii and mostly were found in the nucleus and chloroplast. According to the evolutionary phylogenetic relationship, GrFH were dispersed and classified into seven different groups and shared an ancestry relationship with MtFH. The GrFH gene structure prediction revealed diverse intron-exon arrangements between groups. The FH2 conserved domain was found in all the GrFH distributed on 12 different chromosomes. Moreover, 11 pairs of GrFH transpired segmental duplication. Among them, GrFH4-GrFH7 evolved 35 million years ago (MYA) according to the evolutionary divergence time. Besides, 57 cis-acting regulatory elements (CAREs) motifs were found to play a potential role in plant growth, development, and in response to various abiotic stresses, including cold stress. The GrFH genes mostly exhibited biological processes resulting in the regulation of actin polymerization. The ERF, GATA, MYB, and LBD, major transcription factors (TFs) families in GrFH, regulated expression in abiotic stress specifically salt as well as defense against certain pathogens. The microRNA of GrFH unveiled the regulatory mechanism to regulate their gene expression in abiotic stresses such as salt and cold. One of the most economic aspects of cotton (G.raimondii) is the production of lint due to its use in manufacturing fabrics and other industrial applications. The expression profiles of GrFH in different tissues particularly during the conversion from ovule to fiber (lint), and the increased levels (up-regulation) of GrFH4, GrFH6, GrFH12, GrFH14, and GrFH26 under cold conditions, along with GrFH19 and GrFH26 in response to salt stress, indicated their potential involvement in combating these environmental challenges. Moreover, these stress-tolerant GrFH linked to cytoskeleton dynamics are essential in producing high-quality lint.ConclusionsThe findings from this study can contribute to elucidating the evolutionary and functional characterizations of formin genes and deciphering their potential role in abiotic stress such as cold and salt as well as in the future implications in wet lab.

Exploring the Genetic Underpinnings of Bullying: A Contemporary Analysis of Scholarly Investigations

Since the early 21st century, bullying has been a central focus for scholars, with various forms, such as relational, physical, cyber, and social bullying, receiving extensive attention. However, the role of genetic and hereditary factors in bullying remains underexplored. This study systematically reviews 31 scholarly articles published between January 2000 and December 2021. Articles were selected based on predefined inclusion criteria, including methodological rigor, relevance to genetic influences on bullying, and clear population samples. Data sources included Google Scholar, ResearchGate, SAGE Journals, and ERIC, with keywords such as “bullying and genetics,” “bullying and hereditary,” and “family genetics involvement.” The findings reveal significant associations between genetic predispositions and bullying behaviors. For example, genetic factors were found to account for approximately 70–77% of bullying perpetration and victimization in multiple studies, highlighting a strong hereditary influence. Traits such as impulsivity and aggression, often linked to genetic predispositions, were also shown to interact with environmental factors such as family dynamics and peer relationships, amplifying bullying tendencies. These results underscore the critical role of genetic and hereditary transmission in shaping bullying behaviors across generations. The study emphasizes the need for a multidisciplinary approach that integrates genetic research with environmental interventions to address bullying effectively. Practical implications include the development of targeted anti-bullying programs that consider individual genetic susceptibility alongside fostering supportive family and school environments to reduce the intergenerational transmission of bullying behaviors.

Whole exome sequencing reveals heparan sulfate proteoglycan 2 (HSPG2) as a potential causative gene for kidney stone disease in a Thai family

Kidney stone disease (KSD) is a prevalent and complex condition, with an incidence of 85 cases per 100,000 individuals in Thailand. Notably, over 40% of cases are concentrated in the northeastern region, indicating a potential genetic influence, which is supported by genetic mutations reported in several families by our research group. Despite this, the genetic basis of KSD remains largely unknown for many Thai families. This study aimed to identify the genetic mutation responsible for KSD in a specific Thai family, the UBRS131 family, which includes four affected individuals. Whole exome sequencing was performed, and variant filtering using the VarCards2 program identified 10 potentially causative mutations across 9 genes. These mutations were subjected to segregation analysis among family members and screened in 180 control and 179 case samples using real-time PCR-HRM or PCR-RFLP techniques. Prioritization of these variants using GeneDistiller identified the p.Asp775Glu mutation in the heparan sulfate proteoglycan 2 (HSPG2) gene as the likely causative mutation for KSD in this family. The Asp775 residue is highly conserved across vertebrates, and structural analysis suggests that the Glu775 substitution may disrupt the formation of two crucial hydrogen bonds, potentially altering the mutant protein’s configuration. Immunohistochemistry confirmed the presence of perlecan (HSPG2 protein) in the proximal tubules in nephrons. These findings highlight the significant role of the HSPG2 gene in familial KSD within this study family.

Main genetic entities associated with tooth agenesis.

Tooth agenesis refers to the absence of one or more of the deciduous or permanent teeth. Tooth agenesis results from a series of disrupted reciprocal ectodermal mesenchymal interactions taking place during the early stages of tooth development. A narrative literature review was performed to describe the main genetic syndromes associated with tooth agenesis. The etiology of congenital tooth agenesis is multifactorial and include genetic, epigenetic, and environmental influences. Syndromes associated with chromosomal alterations, ectodermal dysplasia, Axenfeld-Rieger syndrome, oral-facial cleft syndromes, and syndromes with cancer predisposition are among the main entities presenting with tooth agenesis. Tooth agenesis disorders can affect the masticatory function and cause disfigurement leading to physiological and psychological complications. Early recognition of these entities is crucial to guide the management of the patient and to provide families with the appropriate genetic counseling.

Genetic Variants Influence the Severity of Oral Mucositis in Pediatric Osteosarcoma Patients.

The variability in patients' risk of oral mucositis (OM) has been, in part, attributed to differences in host genomics. The aim better define the role of genomics as an OM risk by investigating the association between genetic variants and the presence and severity of OM in pediatric patients with osteosarcoma (OS) undergoing chemotherapy (CT). A longitudinal observational retrospective study was conducted. Severity of OM was assessed daily using World Health Organization (WHO) criteria. Blood samples were collected, and DNA was extracted. 54 coding regions were analyzed for 17 candidate genes using next-generation sequencing. A total of 164 CT cycles were evaluated in 14 pediatric patients being treated for OS with HDMTX (66.9%) and doxorubicin + cisplatin (34.1%). OM was diagnosed in 129 cycles (78.7%). Whereas the presence of OM was associated with ABCA3 (rs13332514) in HDMTX cycles, OM severity was associated with ABCC2 (rs2273697) in multivariate analysis. In doxorubicin + cisplatin, genetic variants of ABC family genes (ABCC2 and ABCC6) were associated with OM in multivariate analysis. Oral mucositis risk and severity in a pediatric population being treated for OS with HDMTX, doxorubicin, and cisplatin were associated with genes in the ABC family (ABCA3, ABCC2, and ABCC6 genes).

Neuroinflammation in Alzheimer disease.

Increasing evidence points to a pivotal role of immune processes in the pathogenesis of Alzheimer disease, which is the most prevalent neurodegenerative and dementia-causing disease of our time. Multiple lines of information provided by experimental, epidemiological, neuropathological and genetic studies suggest a pathological role for innate and adaptive immune activation in this disease. Here, we review the cell types and pathological mechanisms involved in disease development as well as the influence of genetics and lifestyle factors. Given the decade-long preclinical stage of Alzheimer disease, these mechanisms and their interactions are driving forces behind the spread and progression of the disease. The identification of treatment opportunities will require a precise understanding of the cells and mechanisms involved as well as a clear definition of their temporal and topographical nature. We will also discuss new therapeutic strategies for targeting neuroinflammation, which are now entering the clinic and showing promise for patients.

MTHFR Gene Polymorphisms and DNA Methylation in Idiopathic Spontaneous Preterm Birth

Background and Objectives: Preterm birth (PTB) is a complex condition with various contributing factors, including genetic and epigenetic influences such as DNA methylation. Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in DNA methylation and the remethylation of homocysteine. This study aimed to investigate the association between maternal MTHFR C677T and A1298C polymorphisms, LINE-1 DNA methylation levels, and the risk of idiopathic spontaneous preterm birth (SPTB) in Caucasian women from Croatia and Slovenia. Materials and Methods: A total of 50 women with SPTB (<34 weeks of gestation) and 50 control women were included in the study. MTHFR polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and LINE-1 DNA methylation levels were quantified using the MethyLight method. Results: The study found no significant differences in MTHFR C677T and A1298C polymorphisms’ genotype or allele frequencies between women with SPTB and controls. Additionally, no statistical significance of LINE-1 DNA methylation was found between the genotypes of the MTHFR polymorphisms analyzed. Conclusions: The study suggests no conclusive association between MTHFR C677T and A1298C polymorphisms, LINE-1 DNA methylation, and SPTB in Croatian and Slovenian women. Considering prior evidence connecting MTHFR polymorphisms, hyperhomocysteinemia, and PTB, the lack of homocysteine measurements and unassessed impact of folate or vitamin B supplementation limit the conclusions.

Eccentric hypertrophy impairs outcome after TAVR.

Aortic stenosis (AS) induces cardiac remodeling upon chronic left ventricular (LV) pressure overload. Here, we analyzed the clinical outcome of patients undergoing transcatheter aortic valve replacement (TAVR) for symptomatic AS with regard to varying LV hypertrophy patterns. Moreover, we investigated the genetic influence on development of different hypertrophy patterns, measured by polygenic risk scores (PRS). 1703 patients with severe AS undergoing TAVR were categorized according to LV mass index and relative wall thickness in four subgroups: normal geometry (NG, n = 57), concentric remodeling (CR; n = 388), concentric hypertrophy (CH; n = 993) and eccentric hypertrophy (EH; n = 265). Data was analyzed retrospectively with regard to clinical outcome. In a substudy, 520 patients affected by CH (n = 237), EH (n = 139) or CR (n = 164) were analyzed using two PRS that have been previously associated with hypertrophic and dilated cardiomyopathy. 1year after TAVR, for EH, in contrast to the remaining groups (NG, CR, CH), a significant difference in all-cause mortality was observable (mortality 17.4% EH, 14.0% NG, 12.4% CR, 14.0% CH, p = 0.001). This difference was observed up to 4years (mortality 41.9% EH, 26.9% CH, 28.1% CR, 26.4% NG, p = 0.001). Of note, higher percentiles in a PRS for hypertrophic cardiomyopathy were associated with a reduced likelihood of EH in patients with AS (p = 0.046). The EH group had a statistically significant poorer 1-year and 5-year outcomes than the other groups. PRS might help predict myocardial reactions in patients with aortic stenosis in future.

The host genotype actively shapes its microbiome across generations in laboratory mice

BackgroundThe microbiome greatly affects health and wellbeing. Evolutionarily, it is doubtful that a host would rely on chance alone to pass on microbial colonization to its offspring. However, the literature currently offers only limited evidence regarding two alternative hypotheses: active microbial shaping by host genetic factors or transmission of a microbial maternal legacy.ResultsTo further dissect the influence of host genetics and maternal inheritance, we collected two-cell stage embryos from two representative wild types, C57BL6/J and BALB/c, and transferred a mixture of both genotype embryos into hybrid recipient mice to be inoculated by an identical microbiome at birth.ConclusionsObserving the offspring for six generations unequivocally emphasizes the impact of host genetic factors over maternal legacy in constant environments, akin to murine laboratory experiments. Interestingly, maternal legacy solely controlled the microbiome in the first offspring generation. However, current evidence supporting maternal legacy has not extended beyond this initial generation, resolving the aforementioned debate.BvkFmArGExF4DhB6h6D8wqVideo Graphical

Daily estradiol and progesterone levels moderate genetic and environmental influences on emotional eating across 45 consecutive days in female twins.

Past studies indicate daily increases in estrogen across the menstrual cycle protect against binge-eating (BE) phenotypes (e.g. emotional eating), whereas increases in progesterone enhance risk. Two previous studies from our laboratory suggest these associations could be due to differential genomic effects of estrogen and progesterone. However, these prior studies were unable to directly model effects of daily changes in hormones on etiologic risk, instead relying on menstrual cycle phase or mean hormone levels. The current study used newly modified twin models to examine, for the first time, the effects of daily changes in estradiol and progesterone on genetic/environmental influences on emotional eating in our archival twin sample assessed across 45 consecutive days. Participants included 468 female twins from the Michigan State University Twin Registry. Daily emotional eating was assessed with the Dutch Eating Behavior Questionnaire, and daily saliva samples were assayed for ovarian hormone levels. Modified genotype × environment interaction models examined daily changes in genetic/environmental effects across hormone levels. Findings revealed differential effects of daily changes in hormones on etiologic risk, with increasing genetic influences across progesterone levels, and increasing shared environmental influences at the highest estradiol levels. Results were consistent across primary analyses examining all study days and sensitivity analyses within menstrual cycle phases. Findings are significant in being the first to identify changes in etiologic risk for BE symptoms across daily hormone levels and highlighting novel mechanisms (e.g. hormone threshold effects, regulation of conserved genes) that may contribute to the etiology of BE.

Race and ethnicity dynamics in survival to 100 years in the United States.

After age 85, the U.S. non-Hispanic Black population mortality rate becomes less than that of the White population (called the Black-White mortality crossover). It is not known how this survival advantage compares to Asian and Hispanic groups, and whether differences persist to age 100+ years. The U.S. period life table data were extracted to obtain life expectancy at birth and at ages 70, 85, and 100 years according to year, sex, and race and ethnicity. Age-specific death rates and adult modal age at death were calculated. We computed period probabilities of survival to age 100, from ages 70, 80, and 90. Pseudo-birth cohort calculations were undertaken to enable comparison with period-based results. In 2019, the Black-White mortality crossover occurred at 86-88 years and persisted at ages 100 and 100+. Life expectancies at age 100 for non-Hispanic Black, Hispanic, and Asian populations were similar and were significantly greater than the non-Hispanic White population. From 2006 to 2019, the probability of survival from 70 and 80 years to age 100 was highest for the Hispanic population, followed by non-Hispanic Black and then non-Hispanic White populations. Probability of survival from age 90 to 100 years was similar for all but the non-Hispanic White population, which had a comparatively lower probability of survival. When Asian population data became available in 2019, this population had the highest probability of survival to age 100, starting from ages 70, 80, and 90 years. Pseudo-cohort results displayed patterns consistent with those observed over calendar years. Race- and ethnicity-based variation in mortality between ages 85 and 100+ years suggests differences in environmental and possibly genetic influences upon risk for exceptional longevity.

Mapping genes for human face shape: Exploration of univariate phenotyping strategies.

Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.

Exploring the Genetic Contribution in Obesity: an overview of dopaminergic system genes.

Obesity is a widespread global health concern that affects a significant portion of the population and is associated with reduced quality of life, morbidity, and mortality. It is considered a pandemic, with its prevalence constantly rising in Western countries. As a result, numerous studies have focused on understanding the elements that contribute to obesity. Researchers have focused on neurotransmitters in the brain to develop weight management drugs that regulate food intake. This review explores the literature on genetic influences on dopaminergic processes to determine whether genetic variation has an association with obesity in reward-responsive regions, including mesolimbic efferent and mesocortical areas. Various neurotransmitters play an essential role in regulating food intake, such as dopamine which controls through mesolimbic circuits in the brain that modulate food reward. Appetite stimulation, including primary reinforcers such as food, leads to an increase in dopamine release in the reward centers of the brain. This release is related to motivation and reinforcement, which determines the motivational weighting of the reinforcer. Changes in dopamine expression can lead to hedonic eating behaviors and contribute to the development of obesity. Genetic polymorphisms have been investigated due to their potential role in modulating the risk of obesity and eating behaviors. Therefore, it is crucial to assess the impact of genetic alterations that disrupt this pathway on the obesity phenotype.

Exposure to air pollution increases susceptibility to ulcerative colitis through epigenetic alterations in CXCR2 and MHC class III region

This study aims to confirm the associations of air pollution with ulcerative colitis (UC) and Crohn's disease (CD); to explore interactions with genetics and lifestyle; and to characterize potential epigenetic mechanisms. We identified over 450,000 individuals from the UK Biobank and investigated the relationship between air pollution and incident inflammatory bowel disease (IBD). Cox regression was utilized to calculate hazard ratios (HRs), while also exploring potential interactions with genetics and lifestyle factors. Additionally, we conducted epigenetic Mendelian randomization (MR) analyses to examine the association between air pollution-related DNA methylation and UC. Finally, our findings were validated through genome-wide DNA methylation analysis of UC, as well as co-localization and gene expression analyses. Higher exposures to NOx (HR=1.20, 95% CI 1.05-1.38), NO2 (HR=1.19, 95% CI=1.03-1.36), PM2.5 (HR=1.19, 95% CI=1.05-1.36) and combined air pollution score (HR=1.26, 95% CI=1.11-1.45) were associated with incident UC but not CD. Interactions with genetic risk score and lifestyle were observed. In MR analysis, we found five and 22 methylated CpG sites related to PM2.5 and NO2 exposure to be significantly associated with UC. DNA methylation alterations at CXCR2 and sites within the MHC class III region, were validated in genome-wide DNA methylation analysis, co-localization analysis and analysis of colonic tissue. We report a potential causal association between air pollution and UC, modified by lifestyle and genetic influences. Biological pathways implicated include epigenetic alterations in key genetic loci, including CXCR2 and susceptible loci within MHC class III region. Xue Li was supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (No. 82204019). ET was supported by the CRUK Career Development Fellowship (C31250/A22804) and the Research Foundation Flanders (FWO). JW was supported by Belgium by a PhD Fellowship strategic basic research (SB) grant (1S06023N). JKN was supported by the National Science Center, Poland (No. 2020/39/D/NZ5/02720). The IBD Character was supported by the European Union's Seventh Framework Programme [FP7] grant IBD Character (No. 2858546).

Congenital Heart Defects in Paediatric Patients with Congenital Urogenital Abnormalities: A Cross-sectional Study

Introduction: Congenital Heart Defects (CHD) are the most significant co-morbidity in children with congenital anomalies of the kidney and urinary tract, according to past research. The fundamental cause is a combination of certain genetic factors and environmental influences on foetal development. Aim: To investigate the incidence of CHD in congenital urogenital abnormalities in paediatric patients. Materials and Methods: A cross-sectional study was conducted at Dr. D.Y. Patil Medical College, Pune, Maharashtra, India, from June 2023 to December 2023 on 110 patients with congenital urogenital abnormalities undergoing elective surgical procedures to find the incidence of CHDs. All routine investigations, clinical history and examination, ultrasonography, and echocardiography were done. The association of the variables that were quantitative and not normally distributed in nature was analysed using the Mann-Whitney’s Test, and variables that were quantitative and normally distributed in nature were analysed using an independent t-test. The association of variables which were qualitative in nature was analysed using the Fischer’s-exact test. Results: The maternal demographic characteristics that were included were maternal age, gestational age, parity, and consanguinity of marriage. The mean maternal age was 25.65±2.79 years. The mean gestational age was 38.55±1.27 weeks. Consanguinity of marriage was observed in four out of 110 cases. Out of 110 cases, the mean primigravida was 37.27%, gravida 2 was 46.36%, gravida 3 was 13.4%, and gravida 4 was 2.73%. The demographic characteristics of children with urogenital anomalies showed a female-to-male ratio of 50:60. Clinically, a murmur was observed in 15% of cases, and other anomalies were detected in two cases. Out of the total 110 patients with urogenital abnormalities, 15 patients had CHD. Among the 15 cases, four cases were Atrial Septal Defects (ASD), six cases were Patent Ductus Arteriosus (PDA), and five cases were Ventricular Septal Defects (VSD). The total incidence of CHDs was 13.6%. Conclusion: Therefore, authors infered that the incidence of CHD was 13.6% in paediatric patients with congenital urogenital abnormalities. Children with congenital urogenital abnormalities need to be investigated with routine echocardiography. Thus, early diagnosis and therapeutic intervention of CHDs shall not only improve the surgical outcome of congenital urogenital anomalies but also improve the long-term outcome of this highrisk patient population.

The Evolution of Human Intelligence Throughout a Person's Life - A Lifelong Journey

This is an extended article from the book Intelligence, from Natural Origins to Artificial Frontiers - Human Intelligence vs. Artificial Intelligence, by Nicolae Sfetcu. The evolution of human intelligence during a person's lifetime is a process influenced by an interaction between biological development, genetics, environmental factors, and personal experiences. To comprehend the progression of intellectual growth, it is essential to explore the emergence, maturation, and sometimes, the decline of cognitive abilities, illustrating a complex interplay between genetic predispositions and environmental influences.

The Relationship Between Prenatal, Perinatal, and Postnatal Factors and ADHD: The Role of Nutrition, Diet, and Stress.

Attention-Deficit Hyperactive Disorder (ADHD) is a neurobehavioral syndrome affecting children aged 6-17 with symptoms manifesting before age 12. ADHD presents heterogeneously and is associated with various psychiatric disorders. The cause remains elusive, but genetic and environmental factors, brain region maturation delays, and neurotransmitter dysregulation are implicated. Effective treatment requires a multi-disciplinary approach, primarily involving pharmacological and behavioral intervention. Stimulants like methylphenidate and amphetamines are first-line medications, but non-stimulants may be considered for some patients. However, stimulants face challenges related to misuse, dependence, and long-term tolerability issues. The etiology of ADHD involved genetic predisposition, environmental influences, and prenatal, perinatal, and postnatal factors. Prenatal causes encompass maternal diet, alcohol consumption, viral infections, and stress. Postnatal factors include head trauma, meningitis, toxin, nutritional deficiencies, as well as iodine deficiency and hypothyroidism. The gut microbiome's role in ADHD is emerging, influencing neurodevelopment through microbiota-gut-brain axis. Understanding these diverse etiological factors is essential for comprehensive ADHD management.

On the Activity of Students in Mathematics Lessons the Effect of the Pygmalion Effect

The application of mathematical sciences has a great role in the development of society. Mathematical education is a necessary and important part of general education. Therefore, strengthening the mathematical preparation of students is considered the most important task facing secondary schools. Mathematics is taught in a wide range of programs at every level of education in secondary schools. However, it is not perceived in the same way by all students. While some students find mathematics easy to understand, others find it very difficult. There are several reasons for this: poor mastery of mathematical concepts from primary classes, genetic influences, student's lack of independent work, concepts becoming more complex from class to class, age level, environment. We must keep in mind that it is impossible to succeed in life without understanding mathematics. Therefore, it is necessary to look for the cause of difficulties and try to eliminate them. The purpose of the research is to study the impact of the Pygmalion effect on students' performance in mathematics lessons in secondary schools. Using the Pygmalion effect directs students with a poor understanding of mathematics to positive thinking and creates interest in learning mathematics. Many empirical studies also support the predictions of the Pygmalion effect, but it has been found that its effect sizes can vary from low to moderate. As a result of the research, we concluded that applying the Pygmalion effect in teaching mathematics is one of the best ways to achieve success. The research will be useful for mathematics teachers and parents as well as a contribution to the relevant literature.

Advancing Gene Discovery for Substance Use Disorders Using Additional Traits Related to Behavioral Disinhibition.

Substance use disorders (SUDs) frequently co-occur with each other and with other traits related to behavioral disinhibition, a spectrum of outcomes referred to as externalizing. Nevertheless, genome-wide association studies (GWAS) typically study individual SUDs separately. This single-disorder approach ignores genetic covariance between SUDs and other traits and may contribute to the relatively limited genetic discoveries to date. To identify the most effective model for capturing genetic relationships between SUDs and externalizing phenotypes, optimizing the detection of genetic influences on SUDs while maintaining specificity. We used Genomic SEM to estimate SNP effects on a broad factor representing liability to externalizing and SUDs, on factors representing liability to behavioral disinhibition and SUDs separately, and on residualized SUDs. Subsequent gene-based, tissue expression, and polygenic score (PGS) analyses were used to compare the ability of these alternative approaches to identify genetic influences on SUDs. This study was carried out from May 2023 - September 2024. We used GWAS summary statistics based on samples of European ancestry from previous studies of externalizing and SUD phenotypes in the main multivariate GWAS ( N > 2.2 million). We used two independent samples to estimate polygenic associations, a family-based sample enriched for substance use problems (COGA; N = 7,530) and a population-based sample representative of the United States, (All of Us; N = 77,442). N/A. Across the three factors (Externalizing; SUDs; Behavioral Disinhibition) and four residualized SUDs (alcohol, tobacco, opioid, and cannabis), we compared the number, putative function, previous associations of significant genomic risk loci and genes, and variance explained by polygenic scores in substance use outcomes. We identified genomic risk loci and genes uniquely associated with Externalizing that are relevant to the neurobiology of substance use. Genes identified for residual SUDs were involved in substance-specific processes (e.g., metabolism). The Externalizing PGS accounted for the most variance in substance outcomes relative to the PGS for the other factors and residual PGS appeared to capture substance specific signals. Our findings suggest that modeling both a broad genetic liability to externalizing behaviors and substance-specific liabilities enhances the detection of genetic effects related to SUDs and explains more variance in substance use outcomes. Question: Can we advance gene discovery for substance use disorders (SUDs) by incorporating information about correlated outcomes related to behavioral disinhibition?Findings: Combining genetic effects common to SUDs and behavioral disinhibition in a multivariate genome-wide association study of > 2.2 million individuals identified 708 genomic risk loci and accounted for more variance in SUD phenotypes compared with modeling each set of phenotypes separately.Meaning: SUDs and behavioral dysregulation are influenced by a common set of common variants; modeling their joint contributions improves power for genetic discovery and polygenic prediction.