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Background: Numerous studies have explored the association of air pollution with asthma but have yielded conflicting results. The exact role of air pollution in the incidence of adult-onset asthma and whether this effect is modified by genetic risk, lifestyle, or their interaction remain uncertain. Methods: We conducted a prospective cohort study on 298,738 participants (aged 37–73 years) registered in the UK Biobank. Cox proportional hazard models were used to evaluate the association of air pollution, including particulate matter (PM2.5, PMcoarse, and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with asthma incidence. We constructed genetic risk and lifestyle scores, assessed whether the impact of air pollution on adult-onset asthma risk was modified by genetic susceptibility or lifestyle factors, and evaluated the identified interactions. Results: We found that each interquartile range increase in annual concentrations of PM2.5, NO2, and NOx was related to 1.04 (95% confidence interval [CI]: 1.01, 1.08), 1.04 (95% CI: 1.00, 1.08), and 1.03 (95% CI: 1.00, 1.06) times the risk of adult-onset asthma, respectively. The size of the effect of air pollution was greater among subpopulations with low genetic risk or unfavorable lifestyles. We also identified an additive interaction effect of air pollution with lifestyle factors, but not with genetic risk, on the risk of adult-onset asthma. Conclusion: Our analyses show that air pollution increases the risk of adult-onset asthma, but that the size of the effect is modified by lifestyle and genetic risk. These findings emphasize the need for integrated interventions for environmental pollution by the government as well as adherence to healthy lifestyles to prevent adult-onset asthma.

Neural tube defects (NTDs) are serious congenital deformities of the nervous system that occur owing to the failure of normal neural tube closures. Genetic and non-genetic factors contribute to the etiology of neural tube defects in humans, indicating the role of gene-gene and gene-environment interaction in the occurrence and recurrence risk of neural tube defects. Several lines of genetic studies on humans and animals demonstrated the role of aberrant genes in the developmental risk of neural tube defects and also provided an understanding of the cellular and morphological programs that occur during embryonic development. Other studies observed the effects of folate and supplementation of folic acid on neural tube defects. Hence, here we review what is known to date regarding altered genes associated with specific signaling pathways resulting in NTDs, as well as highlight the role of various genetic, and non-genetic factors and their interactions that contribute to NTDs. Additionally, we also shine a light on the role of folate and cell adhesion molecules (CAMs) in neural tube defects.

The timing of primary tooth eruption is critical for children's health planning and the diagnosis of specific growth disorders. The purpose of this study is to assess the relationship between twin pairs' birth weight, gestational age, and gender, which are indicators of prenatal factors; breast-feeding duration, which is an indicator of postnatal factors; type of delivery, which is an indicator of maternal as well as genetic factors; and age of the primary tooth. Twin children aged from 3 to 15 years who applied to the clinic for the first dental examination constituted the sample group. In this twin study, 59 monozygotic (MZ) twin pairs and 143 dizygotic (DZ) twin pairs were included. Genetic (MZ vs. DZ), maternal (type of delivery, gestational age), perinatal (birth weight, gender), and postnatal (duration of breastfeeding) information was obtained, and effects on the children's Eruption Timing of the First Primary Tooth (ETFPT) were examined. Statistical analysis was performed using the consistent partial least squares structural equation model (robust PLSc) technique. As birth weight increased, the age at first eruption became younger, but this change was different between MZ and DZ twins (p < 0.05). While the age at first tooth eruption was older in identical twins who were breastfed for the first 6 months, this increase was not observed in DZ twins. The mean of ETFPT was calculated as 7.31 months in MZ twins and 6.75 months in DZ twins. The effect of breastfeeding and birth weight on ETFPT may differ according to zygosity in twins. MZ twins may tend to take longer to experience the eruption of their first primary teeth. [ABSTRACT FROM AUTHOR]

Background: Vogt‒Koyanagi‒Harada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. Case presentation: A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. Conclusions: To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied. [ABSTRACT FROM AUTHOR]

Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs with high rates of virological clearance. The reduction in cirrhosis-related consequences, particularly HCC, is the long-term objective of DAAs therapy for HCV. Although the risk of developing HCC is decreased in HCV patients who achieve a disease-sustaining virological response, these patients are nevertheless at risk, especially those with severe fibrosis and cirrhosis. Previous studies have shown that HCV induce several mechanisms of hepatocarcinogenesis in the host's hepatic micro- and macro-environment, which leads to HCC progression. In an HCV-altered environment, compensatory liver regeneration favors chromosomal instability and irreversible alterations, which encourage hepatocyte neoplastic transformation and the development of malignant clones. These mechanisms involve a series of genetic and epigenetic modifications including host genetic factors, dysregulation of several signaling pathways, histone, and DNA modifications including methylation and acetylation. This review highlights the genetic and epigenetic factors that lead to the development of HCC in chronic HCV-infected individuals and can be targeted for earlier HCC diagnosis and prevention. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) and osteoporosis are both age-related degenerative diseases. Many studies indicate that these two diseases share common pathogenesis mechanisms. In this review, the osteoporotic phenotype of AD mouse models was discussed, and shared mechanisms such as hormonal imbalance, genetic factors, similar signaling pathways and impaired neurotransmitters were identified. Moreover, the review provides recent data associated with these two diseases. Furthermore, potential therapeutic approaches targeting both diseases were discussed. Thus, we proposed that preventing bone loss should be one of the most important treatment goals in patients with AD; treatment targeting brain disorders is also beneficial for osteoporosis. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) is an autoimmune disease, which can be limited to the skin or associated with systemic lupus erythematosus (SLE). Gene expression analysis has revealed that both the innate and adaptive immune pathways are activated in CLE. Ultraviolet (UV) light, the predominant environmental factor associated with CLE, induces apoptosis in keratinocytes, and the endogenous nucleic acids released from the apoptotic cells are recognized via pattern recognition receptors, including Toll-like receptors. This leads to the production of type I interferon, a major contributor to the pathogenesis of CLE, by plasmacytoid dendritic cells. UV irradiation can also induce the externalization of autoantigens, such as SS-A/Ro, exposing them to circulating autoantibodies. T-helper 1 cells have been reported to play important roles in the adaptive immune response to CLE. Other environmental factors associated with CLE include drugs and cigarette smoke. Genetic factors also confer a predisposition to the development of CLE, and many susceptibility genes have been identified. Monogenetic forms of CLE also exist. This article aims to review current knowledge about the pathogenesis of CLE. A better understanding of the environmental, genetic, and immunoregulatory factors that drive CLE may provide important insights for the treatment of CLE. [ABSTRACT FROM AUTHOR]

Introduction: The co-occurrence between major depression disorder (MDD) and conduct disorder (CD) is common across development and represents a significant risk factor for future psychiatric problems and long-term impairment. Large-scale quantitative genetic studies suggest that the MDD-CD co-occurrence may be partly explained by shared genetic vulnerability factors, in line with transdiagnostic models of psychopathology, but no systematic synthesis of the literature is currently available.Methods: We therefore conducted a systematic review of the available genetic literature on the co-occurrence between MDD and CD in children and adolescents. We identified 10 eligible studies, including 5 cross-sectional bivariate/multivariate twin studies, 3 longitudinal bivariate/multivariate twin studies, and 2 latent profile/trajectory twin studies.Results: Most of the reviewed studies found a strong contribution of shared genetic factors on the covariation between depression and conduct problems, in line with the prominent effect of a common genetic liability across development.Limitations: The scientific literature on this psychiatric comorbidity is still limited, as it solely consists of twin studies from high income countries.Conclusion: Considering the joint burden of MDD and CD on youth, families and society worldwide, future studies are needed to better investigate the shared risk processes of these frequently co-occurring conditions, in order to inform new treatments through personalized medicine. [ABSTRACT FROM AUTHOR]

Cataract (opacification of the ocular lens) is a typical tissue reaction (deterministic effect) following ionizing radiation exposure, for which prevention dose limits have been recommended in the radiation protection system. Manifestations of radiation cataracts can vary among individuals, but such potential individual responses remain uncharacterized. Here we review relevant literature and discuss implications for radiation protection. This review assesses evidence for significant modification of radiation-induced cataractogenesis by age at exposure, sex and genetic factors based on current scientific literature. In addition to obvious physical factors (e.g. dose, dose rate, radiation quality, irradiation volume), potential factors modifying individual responses for radiation cataracts include sex, age and genetics, with comorbidity and coexposures also having important roles. There are indications and preliminary data identifying such potential modifiers of radiation cataract incidence or risk, although no firm conclusions can yet be drawn. Further studies and a consensus on the evidence are needed to gain deeper insights into factors determining individual responses regarding radiation cataracts and the implications for radiation protection. [ABSTRACT FROM AUTHOR]

Both Alzheimer's disease (AD) and primary open angle glaucoma (POAG) are diseases of primary global neurodegeneration with complex pathophysiologies. Throughout the published literature, researchers have highlighted similarities associated with various aspects of both diseases. In light of the increasing number of findings reporting resemblance between the two neurodegenerative processes, scientists have grown interested in possible underlying connections between AD and POAG. In the search for explanations to fundamental mechanisms, a multitude of genes have been studied in each condition, with overlap in the genes of interest between AD and POAG. Greater understanding of genetic factors can drive the research process of identifying relationships and elucidating common pathways of disease. These connections can then be utilized to advance research as well as to generate new clinical applications. Notably, AD and glaucoma are currently diseases with irreversible consequences that often lack effective therapies. An established genetic connection between AD and POAG would serve as the basis for development of gene or pathway targeted strategies relevant to both diseases. Such a clinical application could be of immense benefit to researchers, clinicians, and patients alike. This paper aims to summarize the genetic associations between AD and POAG, describe common underlying mechanisms, discuss potential areas of application, and organize the findings in a review. [ABSTRACT FROM AUTHOR]

Mood and anxiety disorders are complex psychiatric conditions shaped by the multifactorial interplay of genetic, epigenetic, and neuropeptide factors. This review aims to elucidate the intricate interactions among these factors and their potential in advancing personalized medicine. We examine the genetic underpinnings, emphasizing key heritability studies and specific gene associations. The role of epigenetics is discussed, focusing on how environmental factors can modify gene expression and contribute to these disorders. Neuropeptides, including substance P, CRF, AVP, NPY, galanin, and kisspeptin, are evaluated for their involvement in mood regulation and their potential as therapeutic targets. Additionally, we address the emerging role of the gut microbiome in modulating neuropeptide activity and its connection to mood disorders. This review integrates findings from genetic, epigenetic, and neuropeptide research, offering a comprehensive overview of their collective impact on mood and anxiety disorders. By highlighting novel insights and potential clinical applications, we underscore the importance of a multi-omics approach in developing personalized treatment strategies. Future research directions are proposed to address existing knowledge gaps and translate these findings into clinical practice. Our review provides a fresh perspective on the pathophysiology of mood and anxiety disorders, paving the way for more effective and individualized therapies. • Neuropeptides are crucial in gene expression, synaptogenesis, and emotional regulation. • They are involved in stress responses and adjustments, impacting anxiety and depression. • Genetic studies have identified loci related to psychiatric disorders, suggesting shared etiological pathways. • Epigenetic mechanisms, such as microRNAs and histone acetylation, influence antidepressant effectiveness. • Targeting neuropeptide systems and genetic factors shows promise in treating stress-related psychiatric disorders. [ABSTRACT FROM AUTHOR]

Equine osteochondrosis and osteochondral fragments in the fetlock joint are linked to various environmental and genetic risk factors. To assess the scope of the literature linking these risk factors to the development of these osteochondral disorders, while identifying knowledge gaps and challenges to guide future research, a scoping review was performed. This article constitutes the second part of this scoping review and focuses on genetic factors, with the first part addressing environmental factors. To identify potentially relevant papers, online bibliographical databases PubMed and Web of Science were utilised, supplemented with articles listed on the OMIA website (OMIA:000750–9796). After collecting entries, removing duplicates, screening titles, abstracts, and full-text documents for eligibility, and manually searching reference lists of the remaining articles, a total of 212 studies were identified for this scoping review. First, a brief overview of the etiopathogenesis of equine osteochondrosis and osteochondral fragments in the fetlock joint is provided. Subsequently, this article delves into the genetic aspects by presenting an overview of significantly associated quantitative trait loci and potential candidate genes. Next, the challenges in both phenotypic and genomic selection against these osteochondral disorders are discussed, with a focus on the difficulties in phenotyping, the establishment of large and representative reference populations, publication bias, lesion-specific heritabilities, and studbook policies. In conclusion, while there is considerable potential to implement preventive measures that can alleviate the economic burden and enhance animal welfare, further research is necessary. This research should utilize precise and standardized phenotype definitions applied across studies with preferably larger populations. • Scoping review summarising quantitative trait loci andcandidate genes for equine osteochondrosis and fetlock fragments. • Discusses challenges in phenotypic and genomic selection against equine osteochondrosis and fetlock fragments. • Research resource mapping literature, highlighting key studies, and addressing existing gaps and challenges. • Advocates for standardized phenotype definitions and international collaboration to enhance equine selection. • Encourages utilising SNP-chip genotypes for parentage control to support equine selection and research. [ABSTRACT FROM AUTHOR]

Abstract Background Legg–Calvé–Perthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. Although LCPD was first described in the beginning of the past century, limited is known about its etiology. Our objective is to describe the main areas of interest in Legg–Calve–Perthes disease. Methods A review of the literature regarding LCPD etiology was performed, considering the following inclusion criteria: Studies reporting clinical or preclinical results. The research group carried out a filtered search on the PubMed and Science Direct databases. To maximize the suitability of the search results, we combined the terms ‘‘Perthes disease” OR “LCPD” OR “children avascular femoral head necrosis” with “diagnostic” OR “treatment” OR “etiology” as either key words or MeSH terms. Results In this article been described some areas of interest in LCPD, we include topics such as: history, incidence, pathogenesis, diagnosis, treatment and possible etiology, since LCPD has an unknown etiology. Conclusions This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved.

IntroductionThe aim of the present study was to investigate the association between the single nucleotide polymorphism (SNP) rs1927914 A/G in TLR4 gene and the immunological profile of household contacts (HHC) of leprosy patients. Leprosy classification is usually complex and requires the assessment of several clinical and laboratorial features.MethodsHerein, we have applied distinct models of descriptive analysis to explore qualitative/quantitative changes in chemokine and cytokine production in HHC further categorized according to operational classification [HHC(PB) and HHC(MB)] and according to TLR4SNP.Results and discussionOur results showed that M. leprae stimuli induced an outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC(PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-γ; IL-17) were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine signatures demonstrated that A allele was associated with a prominent soluble mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-γ). Data analysis according to TLR4 SNP genotypes further demonstrated that AA and AG were associated with a more prominent secretion of soluble mediators as compared to GG, supporting the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL-6, TNF and IL-17 displayed distinct profiles in HHC(PB) vs HHC(MB) or AA+AG vs GG genotype. In general, chemokine/cytokine networks analysis showed an overall profile of AA+GA-selective (CXCL9–CXCL10) and GG-selective (CXCL10–IL-6) axis regardless of the operational classification. However, mirrored inverted CCL2–IL-10 axis and a (IFN-γ–IL-2)-selective axis were identified in HHC(MB). CXCL8 presented outstanding performance to classify AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17 presented elevated accuracy to classify AA+AG from GG genotypes and HHC(PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted that both factors: i) differential exposure to M. leprae and ii) TLR4 rs1927914 genetic background impact the immune response of HHC. Our main results reinforce the relevance of integrated studies of immunological and genetic biomarkers that may have implications to improve the classification and monitoring of HHC in future studies.

Introduction: Pediatric dermatoses are commonly encountered in the dermatology outpatient department with various presentations in the form of infective and noninfective dermatoses. The incidence and severity of these dermatoses are influenced by geographic, cultural, genetic factors and socioeconomic status. This study was planned to evaluate the burden and pattern of disease among children. Materials and Methods: This was an ambispective observational cohort study, and all the children <12 years of age with noninfectious dermatoses were included from July 2020 to December 2020. Results: We included a total of 1206 pediatric patients in 0-12 years of age with dermatological complaints, of which noninfectious dermatoses were 53% (n = 639) and infectious dermatoses 47% (n = 567). Out of them, 340 (53%) were males and 299 (47%) were females. Among all noninfectious dermatoses, eczema (30%) was found to be the most common dermatosis in our study. Conclusion: The present study focused on noninfectious dermatoses and highlighted the fact that they form a considerable burden of pediatric dermatoses. [ABSTRACT FROM AUTHOR]

The aim of this review was to assess the prevalence and factors related to the metabolic obesity with normal weight (MONW) phenotype. Studies published in English up to December 2021 in the PubMed, Science Direct and Google Scholar databases were searched. The prevalence of MONW is estimated to range from 1.0% to 28.6%, depending on the age of the study participants and the definition of MONW used in the studies. Difficulties in determining the genetic causes of MONW result primarily from the lack of a uniform definition and from the complexity of the disorder. Each component of MONW may be determined by different genes. A person's lifestyle, in particular their diet, seems to be a significant factor in the development of MONW. Studies have so far been unable to determine the optimal type and duration of dietary intervention needed to improve the metabolic parameters in individuals with MONW. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine neoplasms consist of heterogeneous diseases. Depending on the novel features detected by various modern technologies, their classification and related prognosis predictions continue to change and develop. The role of traditional clinicopathological prognostic factors, including classification systems, is also being refined, and several attempts have been made to predict a more accurate prognosis through novel serum biomarkers, genetic factors, and epigenetic factors that have been identified through various state-of-the-art molecular techniques with multiomics sequencing. In this review article, the latest research results including the traditional approach to prognostic factors and recent advanced strategies for risk stratification of pancreatic neuroendocrine neoplasms based on clinical, pathological, and molecular characteristics are summarized. Predicting prognosis through multi-factorial assessments seems to be more efficacious, and prognostic factors through noninvasive methods are expected to develop further advances in liquid biopsy in the future. [ABSTRACT FROM AUTHOR]

Objective: Infertility is a worldwide problem and causes considerable social, emotional and psychological stress between couples and among families. This study is aimed at determining the machine learning classifier capable of developing the most effective predictive model to determine the risk of infertility in men by genetic and external factors. Materials and Methods: The dataset was collected at Ondokuz Mayıs University in the Department of Urology. The model was developed using supervised learning methods and by algorithms like decision tree, K nearest neighbor, Naive bayes, support vector machines, random forest and superlearner. Performances of the classifiers were assessed with the area under the curve. Results: Results of the performance evaluation showed that support vector machines and superlearner algorithms had area under curve of 96% and 97% respectively and this performance outperformed the remaining classifier. According to the results for importance of variables sperm concentration, follicular stimulating hormone and luteinizing hormone and some genetic factors are the important risk factors for infertility. Conclusion: These findings, whenever applied to any patient's record of infertility risk factors, can be used to predict the risk of infertility in men. The predictive model developed can be integrated into existing health information systems which can be used by urologists to predict patients' risk of infertility in real time. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disease with periods of exacerbation and remission of the disease. The etiology of IBD is not fully understood. Many studies point to the presence of genetic, immunological, environmental, and microbiological factors and the interactions between them in the occurrence of IBD. The review looks at genetic factors in the context of both IBD predisposition and pharmacogenetics. [ABSTRACT FROM AUTHOR]

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005–2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy, as a severe microvascular complication of diabetes, manifests in four clinical types: classic, albuminuria regression, a rapid decline in kidney function (RDKF), and non-proteinuric or non-albuminuric DKD. Rapidly progressive diabetic nephropathy advances to end-stage renal disease more swiftly than the typical form, posing significant risks. However, a comprehensive understanding of rapidly progressive diabetic nephropathy is currently lacking. This article reviewed latest developments in genetic and clinical risk factors associated with rapidly progressive diabetic nephropathy, aiming to broad perspectives concerning the diagnosis and interventions of this condition.

Background: Schizophrenia varies greatly from person to person, mainly because of its polygenic nature. Consequently, schizophrenia patients form distinct subphenotypes of schizophrenia, with specific symptom patterns and outcomes., Methods: This study included 4257 adults, with long-term schizophrenia (control - 8955 individuals) who were assessed for schizophrenia with potentially severe outcomes based on following criteria: disability in functional and/or physical domains before the age of 40; severe negative symptoms (present in infancy or shortly after onset); a continuous course of the disease. Additionally, the time of the onset and aggressive/antisocial tendencies were assessed as one the predictors of potentially severe outcomes. A total of 817 participants met at least three of these criteria, i.e., had disruptive schizophrenia. A genome-wide and transcriptome-wide association study was conducted using linear regression and the PrediXcan algorithm. The obtained data were used to develop a polygenic risk model for early risk prediction of schizophrenia with potentially severe outcomes., Results: Significant associations were found between schizophrenia and variants in CAMTA1, TRHDE, NELFE, and others. The PRS model demonstrated high performance in training, internal and external validation (ROC AUC of 0.9, 0.89, and 0.68, respectively). The functional pathway analysis highlighted pathways involved in ATP metabolism, myeloid cell differentiation, and apoptotic processes., Conclusion: Subphenotyping schizophrenia may enhance the discovery of genetic factors affecting its development and progression. The GWAS and TWAS findings revealed general mechanisms involved in the development of schizophrenia with potentially severe outcomes, such as synapse regulation, inflammation, and apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Joseph A Boscarino,1 Richard E Adams,2 Thomas G Urosevich,3 Stuart N Hoffman,4 H Lester Kirchner,1 Xin Chu,5 Weixing Shi,5 Joseph J Boscarino,6 Ryan J Dugan,1 Carrie A Withey,1 Charles R Figley7 1Department Population Health Sciences, Geisinger Clinic, Danville, PA, 17822, USA; 2Department Sociology, Kent State University, Kent, OH, 44242, USA; 3Ophthalmology Service, Geisinger Clinic, Mount Pocono, PA, 18344, USA; 4Department Sleep Medicine, Geisinger Clinic, Danville, PA, 17822, USA; 5Obesity Institute, Geisinger Clinic, Danville, PA, 17822, USA; 6Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, STC 7, Tampa, FL, 33606, USA; 7School of Social Work, Tulane University, New Orleans, LA, 70112, USACorrespondence: Joseph A BoscarinoDepartment Population Health Sciences, Geisinger Clinic, 100 N. Academy Ave., 44-00, Danville, PA, 17822, USATel +1 570-214-9825Email joseph.boscarino@gmail.comIntroduction: Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans.Methods: For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0– 8, mean=3.6, SD=1.4).Results: Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p< 0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p< 0.001), history of depression (p> 0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant.Discussion: In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.Keywords: veterans, warzone deployment, suicide, genetic factors, patient screening, precision medicine

Congenital heart disease (CHD) is the most frequently reported cause among miscarriages. Moreover, Infants born with CHD suffer from lifelong morbidity and have high risk of sudden infant death. The incidence of CHD is 8:1000, around 1% of live births worldwide. A wide range of environmental risk factors such as exposure to teratogens increase the risk for CHD through alterations in genetic and epigenetic networks governing heart development. Yet, a small subset of CHD is caused by inherited Mendelian mutations, copy number variations, or chromosomal abnormalities. Next generation sequencing technologies and chromosomal microarray analysis deciphered the genetic make-up of CHD. This review explains the genetic make-up of CHD and highlights key molecular genetics, cytogenetics, and epigenetics findings in syndromic and isolated CHD through analysis of inherited and sporadic genomic alterations.

Abstract Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value

Background and Objectives: Pain is the most leading cause of visits to physicians and dentists. It is also a common symptom of diseases that can significantly undermine the quality of life and physical activities. This study aimed to review the existing literature for the causes of temporomandibular disorders (TMD) from the genetic point of view. Materials and Methods: Four international scientific databases including Google Scholar, Biomed Central, PubMed, and ProQuest plus two Iranian databases including Magiran and SID. Then all articles published between 1980 and 2019 were searched using the following keywords: facial pain, genetic factors and temporomandibular disorders (TMDs). A total of 900 articles were found that 36 were review articles. Results: Our review shows that genetic factors have an impact on the incidence and pathology of TMDs These factors include TSPAN9 polymorphism and the COMT gene. Conclusion: There is growing evidence indicating that genetic factors play a key role in the pathology of temporomandibular disorders, however, the underlying mechanism of pain is still largely unknown. Keywords: Facial pain; Genetic factors; Temporomandibular joint disorder (TMD).

The etiology of intervertebral disc degeneration (IVDD) is complex and multifactorial, and it is still not fully understood. A better understanding of the pathogenesis of IVDD will help to improve treatment regimens and avoid unnecessary surgical aggression. In order to summarize recent research data on IVDD pathogenesis, including genetic and immune factors, a literature review was conducted. The pathogenesis of IVDD is a complex multifactorial process without an evident starting point. There are extensive data on the role of the different genetic factors affecting the course of the disease, such as mutations in structural proteins and enzymes involved in the immune response. However, these factors alone are not sufficient for the development of the disease. Nevertheless, like mechanical damage, they can also be considered risk factors for IVDD. In conclusion, currently, there is no consensus on a single concept for the pathogenesis of IVDD. We consider the intervertebral disc autoimmune damage hypothesis to be the most promising hypothesis for clinicians, because it can be extrapolated to all populations and does not counteract other factors. The genetic factors currently known do not allow for building effective predictive models; however, they can be used to stratify the risks of individual populations.

The development of antibiotic resistance in Staphylococcus aureus, particularly in methicillin-resistant S. aureus (MRSA), has become a significant health concern worldwide. The acquired mecA gene encodes penicillin-binding protein 2a (PBP2a), which takes over the activities of endogenous PBPs and, due to its low affinity for β-lactam antibiotics, is the main determinant of MRSA. In addition to PBP2a, other genetic factors that regulate cell wall synthesis, cell signaling pathways, and metabolism are required to develop high-level β-lactam resistance in MRSA. Although several genetic factors that modulate β-lactam resistance have been identified, it remains unclear how they alter PBP2a expression and affect antibiotic resistance. This review describes the molecular determinants of β-lactam resistance in MRSA, with a focus on recent developments in our understanding of the role of mecA-encoded PBP2a and on other genetic factors that modulate the level of β-lactam resistance. Understanding the molecular determinants of β-lactam resistance can aid in developing novel strategies to combat MRSA.

Gilbert's syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been conducted on Caucasian populations. In this study, we studied the Han population in Taiwan to investigate the possibility of other mutations that could cause Gilbert's syndrome. This study comprised a test group of 45 Taiwanese individuals with Gilbert's syndrome and 180 healthy Taiwanese individuals as a control group. We extracted DNA from the blood samples and then used Axiom Genome-Wide TWB 2.0 array plates for genotyping. Out of 302,771 single nucleotide polymorphisms (SNPs) from 225 subjects, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in the UGT1A region. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input for the machine learning algorithms and developed prediction models. Our study reveals a good association between the 27 SNPs detected and Gilbert's syndrome. Hence, this study provides a reference for diagnosing Gilbert's syndrome in the Taiwanese population in the future. [ABSTRACT FROM AUTHOR]

This study Orginal investigated the diagnosis and treatment of MS in patients (111 Patients) with various degrees of the disease with a clinical approach. MS is an autoimmune disease in which the body's immune system attacks its own tissues. In MS, the malfunctioning immune system destroys myelin. Myelin is a fatty substance that covers and protects the nerve fibers of the brain and spinal cord. When the protective myelin sheath is damaged and nerve fibers are exposed, the speed at which messages are transmitted along the nerve slows or is blocked. The concordance rate for MS in monozygotic identical twins is only 20-35%, indicating that genetic factors have only a moderate effect and transmission is not 100%. The presence of non-Mendelian predisposing factors along with environmental effects plays an important role. For first-degree family members of people with MS, the risk of developing the disorder is seven times greater than in the general population, but the excess family risk for the disease is only 2.5-5%. Research on single nucleotide polymorphisms that play a role in the risk of developing severe disease or developing certain types of MS is ongoing. To date, however, HLA-DRB1 is the only chromosomal locus consistently associated with MS susceptibility. Molecular mimicry has been proposed as an etiological process in MS. The molecular mimicry hypothesis suggests that T cells in peripheral blood may, after being activated to attack a foreign antigen, then mistakenly continue to attack proteins in the brain that have similar epitopes. [ABSTRACT FROM AUTHOR]

Background: The renin–angiotensin system (RAS), which is important for controlling haemostasis in the body, can increase the development of essential hypertension (HTN). Various surveys have shown that ACE I/D polymorphism that influences ACE activity, a key component of RAS, has been known to be associated with the risk of HTN. The goal of this study was to investigate the correlation between ACE (I/D) polymorphism and HTN. Methods: Blood samples were obtained from 102 patients and 104 healthy individuals. The two groups were matched by age and sex. Informed consent was prepared for the study. The demographic data were collected using a questionnaire. White blood cells (WBCs) and then DNA were extracted from whole blood. After this, the PCR test was performed using specific primers. PCR products were examined using 1% agarose gel. Individuals with genotype II having a band of 490 bp, ID two band of 490 bp and 190 bp, and individuals with DD genotype, have a band in region 190 bp. Results: The average age of the patients was 52.7 ± 7.5 years. A significant difference was seen in the distribution of DD, II and I/D genotypes of ACE polymorphism between the essential hypertensive patients (44.1, 10.8, and 45.1%) and their ethnically matched healthy control (61.5, 3.8, and 24.6%, respectively). Our study showed an increased risk of disease in people with II genotype in comparison to ID and DD genotypes (0.46 (0.1–1.75) and 0.26 (0.05–0.94), respectively). Conclusions: The present study demonstrated that ACEI/D polymorphism is characterised with greater risk of essential HTN in the Lorestan province. II genotype increased the relative risk of essential HTN in the population. In the future, more investigations with more samples size are recommended for the better study of genetic factors in hypertensive patients. [ABSTRACT FROM AUTHOR]

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Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common systemic vasculitis in children, characterized by diverse clinical manifestations with a wide spectrum ranging from isolated cutaneous vasculitis to systemic involvement. The incidence of IgAV is geographically and ethnically variable, with a prevalence in autumn and winter, suggesting a driving role that genetic and environmental factors play in the disease. Although IgAV has a certain degree of natural remission, it varies widely among individuals. Some patients can suffer from severe renal involvement and even progress to end-stage renal disease. Its pathogenesis is complex and has not been fully elucidated. The formation of galactosedeficient IgA1 (Gd-IgA1) and related immune complexes plays a vital role in promoting the occurrence and development of IgAV nephritis. In addition, neutrophil activation is stimulated through the binding of IgA to the Fc alpha receptor I expressed on its surface, resulting in systemic vascular inflammation and tissue damage. Starting from the epidemiological characteristics, this article will review the role of immunological factors such as Gd-IgA1, autoantibodies, circulating immune complexes, complement system, cellular immunization, and the contributions of environmental and genetic factors in the pathogenesis of IgAV, and conclude with the major biomarkers for IgAV. [ABSTRACT FROM AUTHOR]

We explored the genetic and environmental inter-relationships among osteoporosis, fracture, arthritis, and bone mineral density concordance in monozygotic twins compared to those in dizygotic twins. This cross-sectional research assessed data of 1032 monozygotic and 242 dizygotic twin pairs aged >20 years included in the Healthy Twin Study data of the Korean Genome and Epidemiology Study between 2005 and 2014. Outcomes of interest included illness concordance and absolute differences in dual-energy X-ray absorptiometry (DEXA) T-scores. We found comparable concordances of osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis between monozygotic and dizygotic twins. Medical histories of osteoporosis, fractures caused by accident or falling, osteoarthritis, and rheumatoid arthritis were not distinct between monozygotic and dizygotic twins. Accidental fracture occurrence in both monozygotic twins showed significantly lower odds than that in dizygotic twins. Genetic influence on liability to fracture risk might thus be maintained. DEXA T-scores for bone mineral density indicated more comparable tendencies within monozygotic twin pairs than within dizygotic ones, suggesting the relative importance of genetic contribution to bone mineral density. The relative importance of genetic factors in bone mineral density is sustained between monozygotic twins; overt disease expression of osteoporosis, fractures, or arthritis may be affected by environmental factors. [ABSTRACT FROM AUTHOR]

Background: A family history of arterial hypertension is an important risk factor for arterial hypertension. This study aimed to verify the mediating role of high central adiposity in the relationship between family history of arterial hypertension and blood pressure in schoolchildren.Methods: Cross-sectional study with 118 schoolchildren of both sexes aged between 11 and 17 years. Weight, height, waist circumference and body mass index z score were verified. Somatic maturation was predicted by age for peak growth velocity. The family history of arterial hypertension was verified and defined as hypertensive schoolchildren with systolic blood pressure or diastolic blood pressure. Mediation analysis was used with linear regression models applied by PROCESS macro for SPSS (version 22.0), with significance p < 0.05.Results: It was observed that 34.7% of the students have family history of arterial hypertension, 36% of the girls and 44.2% of the boys have arterial hypertension. In girls, the relationship between waist circumference and systolic blood pressure was direct (β = 0.535 p = 0.005), and those with a family history of arterial hypertension and who had a waist circumference greater than those without a family history of arterial hypertension was significant (β = -5,437 p = 0.009). Likewise, the relationship between family history of arterial hypertension and systolic blood pressure was attenuated when waist circumference was included in the model (β = -5.544; p = 0.103), indicating waist circumference as a mediator with an influence percentage of 19%. For boys, waist circumference is not a mediator of the relationship between family history of arterial hypertension and blood pressure.Conclusions: Elevated central adiposity was a mediator of the relationship between family history of arterial hypertension and high blood pressure in girls, indicating the importance of family health strategies in the prevention and management of arterial hypertension in children and adolescents. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a grievous neurodegenerative disease whose survival is limited to only a few years. In spite of intensive research to discover the underlying mechanisms, the results are fairly inconclusive. Multiple hypotheses have been regarded, including genetic, molecular, and cellular processes. Notably, oxidative stress has been demonstrated to play a crucial role in ALS pathogenesis. In addition to already recognized and exhaustively studied genetic mutations involved in oxidative stress production, exposure to various environmental factors (e.g., electromagnetic fields, solvents, pesticides, heavy metals) has been suggested to enhance oxidative damage. This review aims to describe the main processes influenced by the most frequent genetic mutations and environmental factors concurring in oxidative stress occurrence in ALS and the potential therapeutic molecules capable of diminishing the ALS related pro-oxidative status. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is a very heterogenic chronic autoimmune disease caused by the failure of neuromuscular transmission. The HLA gene complex has conventionally been recognized as its main genetic risk and phenotype modifying factor. Our aim was to investigate the prevalence of HLA class I and II alleles and to identify possible risk factors for sporadic MG in a Spanish cohort. Methods: We designed a clinical case–control study comparing HLA alleles and haplotype frequencies in a cohort of 234 patients with sporadic autoimmune MG with data from a group of 492 randomly selected healthy subjects. Using a high-resolution next-generation sequencing (NGS)–based HLA genotyping assay, we investigated the contribution of HLA genotypes and haplotypes in the resulting phenotype, especially, the age at onset, sex, onset MGFA class, thymic histopathology, and serological status. Results: We found that the DQB1*05:02 and DQB1*05:03 alleles could be novel risk factors for Spanish MG cases. The HLA alleles A*01:01, B*08:01, DRB1*03:01, DRB1*14:54, and DQB1*02:01 were also risk factors for the disease. DQB1*03:01 acted as a risk factor for EOMG in women with AChR-positive antibodies and thymus hyperplasia. Additionally, several alleles were identified as potential phenotype-modifying factors that could exert a protective effect: HLA-B*35:08, DRB1*13:01, and DQB1*06:03 in MG; HLA-A*24:02 in women and DRB1*07:01 and DQB1*02:02 for early onset. HLA-C*07:01 and haplotype A1-B8-C7-DR3-DQ2 were associated with an early-onset phenotype. [ABSTRACT FROM AUTHOR]

Abstract Background Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association. Methods The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment. Results A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age. Conclusions A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.