Applications of Polygenic Risk Scores in Psychiatric Genetics.

Polygenic risk score (PRS) is a powerful tool for studying the genetic architecture of complex diseases, including psychiatric disorders. This review highlights the use of PRS in psychiatric genetics, including its application in identifying high-risk individuals, estimating heritability, assessing shared etiology between phenotypes, and personalizing treatment plans. It also explains the methodology for calculating PRS, the challenges associated with their use in clinical settings, and future research directions. The main limitation of PRS is that the current models only account for a small fraction of the heritability of psychiatric disorders. Despite this limitation, PRS represents a valuable tool that has already yielded important insights into the genetic architecture of psychiatric disorders.

RNA m6A methylation in psychiatric disorders.

This comprehensive review introduces the features of m6A modification and its role in neuropsychiatric disorders. The research findings suggest that m6A modifications and their regulators play a critical role in the occurrence and development of major psychiatric disorders, especially Alzheimer's disease, affecting synaptic protein synthesis, subtype classification, immune infiltration, pathogenesis, and inflammatory infiltration. These findings highlight m6A regulators as potential new diagnostic and therapeutic targets, with m6A methyltransferase METTL3 being the best-characterized regulator in these diseases. The review concludes that m6A modification is a promising target for the prevention and treatment of major psychiatric disorders.

Spatial Multiomics Analysis in Psychiatric Disorders.

The aim of this study is to provide a comprehensive overview of spatial multiomics analysis, including its definition, processes, applications, significance and relevant research in psychiatric disorders. To achieve this, a literature search was conducted, focusing on three major spatial omics techniques and their application to three common psychiatric disorders: Alzheimer's disease (AD), schizophrenia, and autism spectrum disorders. Spatial genomics analysis has revealed specific genes associated with neuropsychiatric disorders in certain brain regions. Spatial transcriptomics analysis has identified genes related to AD in areas such as the hippocampus, olfactory bulb, and middle temporal gyrus. It has also provided insight into the response to AD in mouse models. Spatial proteogenomics has identified autism spectrum disorder (ASD)-risk genes in specific cell types, while schizophrenia risk loci have been linked to transcriptional signatures in the human hippocampus. In summary, spatial multiomics analysis offers a powerful approach to understand AD pathology and other psychiatric diseases, integrating multiple data modalities to identify risk genes for these disorders. It is valuable for studying psychiatric disorders with high or low cellular heterogeneity and provides new insights into the brain nucleome to predict disease progression and aid diagnosis and treatment.

A significant, functional and replicable risk KTN1 variant block for schizophrenia.

Cortical and subcortical structural alteration has been extensively reported in schizophrenia, including the unusual expansion of gray matter volumes (GMVs) of basal ganglia (BG), especially putamen. Previous genome-wide association studies pinpointed kinectin 1 gene (KTN1) as the most significant gene regulating the GMV of putamen. In this study, the role of KTN1 variants in risk and pathogenesis of schizophrenia was explored. A dense set of SNPs (n = 849) covering entire KTN1 was analyzed in three independent European- or African-American samples (n = 6704) and one mixed European and Asian Psychiatric Genomics Consortium sample (n = 56,418 cases vs. 78,818 controls), to identify replicable SNP-schizophrenia associations. The regulatory effects of schizophrenia-associated variants on the KTN1 mRNA expression in 16 cortical or subcortical regions in two European cohorts (n = 138 and 210, respectively), the total intracranial volume (ICV) in 46 European cohorts (n = 18,713), the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258), and the surface areas (SA) and thickness (TH) of whole cortex and 34 cortical regions in 50 European cohorts (n = 33,992) and eight non-European cohorts (n = 2944) were carefully explored. We found that across entire KTN1, only 26 SNPs within the same block (r2 > 0.85) were associated with schizophrenia across ≥ 2 independent samples (7.5 × 10-5 ≤ p ≤ 0.048). The schizophrenia-risk alleles, which increased significantly risk for schizophrenia in Europeans (q < 0.05), were all minor alleles (f < 0.5), consistently increased (1) the KTN1 mRNA expression in 12 brain regions significantly (5.9 × 10-12 ≤ p ≤ 0.050; q < 0.05), (2) the ICV significantly (6.1 × 10-4 ≤ p ≤ 0.008; q < 0.05), (3) the SA of whole (9.6 × 10-3 ≤ p ≤ 0.047) and two regional cortices potentially (2.5 × 10-3 ≤ p ≤ 0.042; q > 0.05), and (4) the TH of eight regional cortices potentially (0.006 ≤ p ≤ 0.050; q > 0.05), and consistently decreased (1) the BG GMVs significantly (1.8 × 10-19 ≤ p ≤ 0.050; q < 0.05), especially putamen GMV (1.8 × 10-19 ≤ p ≤ 1.0 × 10-4; q < 0.05, (2) the SA of four regional cortices potentially (0.010 ≤ p ≤ 0.048), and (3) the TH of four regional cortices potentially (0.015 ≤ p ≤ 0.049) in Europeans. We concluded that we identified a significant, functional, and robust risk variant block covering entire KTN1 that might play a critical role in the risk and pathogenesis of schizophrenia.

Domestic Violence in Single- and Multi-child families in China: a ten-year comparison in the same communities.

Chinese one-child policy has been practiced for more than 30 years. With the policy that one couple can have two children being fully implemented from Jan 1, 2016 in China, the families with two or more children are increasing, and the family size, family structure and family relationship has been largely changed. Little is known about the difference in domestic violence (DV) among single- and multi-child families in China. This study compared the prevalence, causes, patterns, consequence of DV and the attitude towards DV among single-child and multi-child families in the same communities between ten years in China. Epidemiological surveys were conducted among single-child and multi-child families in the same communities during the period of 2001-2002 (group 2002) for 9451 families and 2011-2012 (group 2012) for 6859 families, respectively. The same investigation methods, questionnaires and investigators were used in the two surveys. The findings indicated that the child abuse has been increasing, and the child education being the issue has climbed to the top in multi-child families. The negative attitude towards DV stayed the same in both single- and multi-child families. It is suggested that the intervention strategies on DV should be adjusted to the new situations, especially with the arrival of more multi-child families in current China.

Effective intervention in domestic violence in Chinese communities: an eight-year prospective study.

BACKGROUND: Domestic violence is increasing in China. To explore the effective intervention, we intervened three large independent Chinese communities with different approaches over an eight-year period from 2005 to 2012, with a fourth independent community as a peer control. METHODS: The intervention approaches included the psychological intervention with traditional Chinese culture characteristics, the social governance and the poverty relief. The statistical analysis was performed in 2017. RESULTS: We found that while the prevalence of domestic violence kept growing in the control community, it significantly declined in the other three target communities. Among these intervention approaches, the social governance was the most effective, whereas it resulted in the lowest happiness index. CONCLUSION: This continuous, long-period, prospective and large-scale study showed that these approaches could significantly reduce domestic violence.

Distribution and flux of organochlorine pesticides in sediment from Prydz Bay, Antarctic: Implication of sources and trends.

Surface sediments were collected from Prydz Bay, Antarctica to investigate the distribution patterns, origins, annual fluxes, and trends of organochlorine pesticides (OCPs) in the marginal sea of polar areas. The concentrations of OCPs ranged from 0.80 to 7.90 ng/g dry weight, with dichlorodiphenytrichloroethanes (DDTs) as the main components. Levels of hexachlorocyclohexanes (HCHs) and DDTs in sediment from Prydz Bay were comparable to the majority of marine sediment worldwide. The distributions of OCPs were characterized by a distinct "quasi-concentric circle" pattern, which has significantly positive relationship with total organic carbon (TOC) of sediment and controlled by the local hydrodynamic conditions and sources of organic matter. Source apportionment demonstrated that HCHs and chlordanes in Prydz Bay were mainly derived from the long range atmospheric transport (LRAT) of these compounds from off regions. However, current inputs of DDT-based compounds and lindane are suggested to exist either as a result of the LART from the neighbouring countries or re-emission from melting glacier. The annual sedimentary fluxes of OCPs were 0.007 to 7.12 pg/cm2/yr, about one to three orders of magnitude lower than some data from the Arctic areas. Based on a rough calculation of r-HCH, only 0.3-1.5% of the air-seawater net deposition would be buried in sediment, implying a long active lifetime of OCPs in Antarctica. We preliminarily indicate an increase of OCP contamination in Antarctic environment afterwards when considering the possible occurrence of "fresh" sources and low proportion of sedimentary sink.

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson's Disease.

BACKGROUND: Selective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson's disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV. OBJECTIVE: To examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD. METHODS: We examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts. RESULTS: Six replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ ß ≤ 60.38; 2.82 ≤ Z ≤ 15.03; 5.0 × 10-51 ≤ p ≤ 0.018). The risk alleles of five SNPs, including rs8017172, rs17253792, rs945270, rs4144657, and rs1188184 also significantly increased the KTN1 mRNA expression in the putamen or SNc (0.021 ≤ p ≤ 0.046). The KTN1 mRNA was abundant in the putamen and/or SNc across five independent cohorts and differentially expressed in the SNc between PD and HC in one cohort (p = 0.047). CONCLUSION: There was a consistent, significant, replicable, and robust positive relationship among the KTN1 variants, PD risk, KTN1 mRNA expression in putamen, and putamen volumes, and a modest relation between PD risk and KTN1 mRNA expression in SNc, suggesting that KTN1 may play a functional role in the development of PD.

Putamen gray matter volumes in neuropsychiatric and neurodegenerative disorders.

Putamen is enriched with dopamine and associated with dopamine-related phenotypes including many neuropsychiatric and neurodegenerative disorders that manifest with motor impairment, impulsive behavior, and cognitive deficits. The gray matter volume of the putamen is age-dependent and genetically controlled. In most neuropsychiatric and neurodegenerative disorders, including Parkinson's spectrum disorders, Huntington's disease, dementia with Lewy bodies, Alzheimer's disease, multiple sclerosis, attention deficit hyperactivity disorder, developmental dyslexia, and major depression, the putamen volume is significantly reduced. On the other hand, in individuals with bipolar disorder, schizophrenia spectrum disorders, especially neuroleptics-medicated patients with schizophrenia, autism spectrum disorders, obsessive-compulsive spectrum disorders, and cocaine/amphetamine dependence, the putamen volume is significantly enlarged. Therefore, the putamen volume may serve as a structural neural marker for many neuropsychiatric and neurodegenerative disorders and a predictor of treatment outcomes in individuals afflicted with these conditions. We provided an overview of the genetic bases of putamen volume and explored potential mechanisms whereby altered putamen volume manifests in these neuropsychiatric and neurodegenerative conditions, with a specific focus on dopaminergic processes.

Transcriptome-wide piRNA profiling in human brains for aging genetic factors.

OBJECTIVE: Piwi-interacting RNAs (piRNAs) represent a molecular feature shared by all nonaging biological systems, including the germline and somatic cancer stem cells, which display an indefinite renewal capacity and lifespan-stable genomic integrity and are potentially immortal. Here, we tested the hypothesis that piRNA is a critical genetic determinant of aging in humans. METHODS: Expression of transcriptome-wide piRNAs (n=24k) was profiled in the human prefrontal cortex of 12 subjects (84.9±9.5, range 68-100, years of age) using microarray technology. We examined the correlation between these piRNAs' expression levels and age, adjusting for covariates including disease status. RESULTS: A total of 9,453 piRNAs were detected in brain. Including seven intergenic and three intronic piRNAs, ten piRNAs were significantly associated with age after correction for multiple testing (|r|=0.9; 1.9×10-5≤p≤9.9×10-5). CONCLUSION: We conclude that piRNAs might play a potential role in determining the years of survival of humans. The underlying mechanisms might involve the suppression of transposable elements (TEs) and expression regulation of aging-associated genes.

Transcriptome­wide piRNA profiling in human gastric cancer.

Piwi­interacting RNAs (piRNAs) comprise the largest class of non­coding RNAs. They represent a molecular feature shared by all non­aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non­tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome­wide significant and replicated cancer­risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2­fold change) expressed between the cases and controls, and 64.7% of the protein­coding genes potentially regulated by the gastric cancer­associated piRNAs were expressed in the human stomach. The expression of many cancer­associated piRNAs was correlated with the genome­wide and replicated cancer­risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.

A bibliometric and social network analysis of pelvic organ prolapse during 2007-2016.

BACKGROUND: Pelvic organ prolapse (POP) seriously affects the life quality of old females. In the present work, we described the knowledge structure of POP in a macroscopic view, and summarized the recent research focus. METHODS: Candidates were identified through reading and screening publications from PubMed database with a MeSH term of "pelvic organ prolapse" during 2007-2016. Relevant journals and journal-affiliated countries were extracted, and essential information, such as the number of publication of each year, first authors and MeSH/subheading words, was analyzed with BICOMB. In addition, highly-frequent MeSH/subheading words were determined and classified, and co-occurrence matrices were produced accordingly. Finally, social network was utilized to analyze the knowledge structure. RESULTS: A total of 3294 publications of POP were retrieved from 364 journals. The publication of POP had a significant downward trend since the beginning of 2015. POP articles published in American and British journals were significantly more compared with other countries. The co-occurrence matrices of 37 × 37 and 55 × 55 were produced by the highly-frequent MeSH/subheading words, and then the social network analysis was performed based on them. CONCLUSION: These publications on POP were mainly from the developed countries. Surgical treatment of POP was a hot topic of POP research in recent 10 years.

Systematic Analysis of Bottlenecks in a Multibranched and Multilevel Regulated Pathway: The Molecular Fundamentals of l-Methionine Biosynthesis in Escherichia coli.

To produce chemicals and fuels from renewable resources, various strategies and genetic tools have been developed to redesign pathways and optimize the metabolic flux in microorganisms. However, in most successful cases, the target chemicals are synthesized through a linear pathway, and regular methodologies for the identification of bottlenecks and metabolic flux optimization in multibranched and multilevel regulated pathways, such as the l-methionine biosynthetic pathway, have rarely been reported. In the present study, a systematic analysis strategy was employed to gradually reveal and remove the potential bottlenecks limiting the l-methionine biosynthesis in E. coli. 80 genes in central metabolism and selected amino acids biosynthetic pathways were first repressed or upregulated to probe their effects on l-methionine accumulation. The l-methionine biosynthetic pathway was then modularized and iteratively genetic modifications were performed to uncover the multiple layers of limitations and stepwise improve the l-methionine titer. The metabolomics data further revealed a more evenly distributed metabolic flux in l-methionine biosynthesis pathway of the optimal strain and provided valuable suggestions for further optimization. The optimal strain produced 16.86 g/L of l-methionine in 48 h by fed-batch fermentation. This work is the first to our knowledge to systematically elucidate the molecular fundamentals of multilevel regulation of l-methionine biosynthesis. It also demonstrated that the systematic analysis strategy can boost our ability to identify the potential bottlenecks and optimize the metabolic flux in multibranched and multilevel regulated pathways for the production of corresponding chemicals.

Association of catechol-O-methyltransferase Val(108/158) Met genetic polymorphism with schizophrenia, P50 sensory gating, and negative symptoms in a Chinese population.

Catechol-O-methyltransferase (COMT), an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, is associated with the sensory gating phenomenon, protecting the cerebral cortex from information overload. The COMT Val(108/158)Met polymorphism is essential for prefrontal cortex processing capacity and efficiency. The current study was designed to investigate the role of COMT Val(108/158)Met polymorphism in development, sensory gating deficit, and symptoms of schizophrenia in Han Chinese population. P50 gating was determined in 139 schizophrenic patients and 165 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptomatology in 370 schizophrenic subjects. COMT Val(108/158)Met polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). No significant differences in COMT allele and genotype distributions were observed between schizophrenic patients and control groups. Although P50 deficits were present in patients, there was no evidence for an association between COMT Val(108/158)Met polymorphism and the P50 biomarker. Moreover, PANSS negative subscore was significantly higher in Val allele carriers than in Met/Met individuals. The present findings suggest that COMT Val(108/158)Met polymorphism may not contribute to the risk of schizophrenia and to the P50 deficits, but may contribute to the negative symptoms of schizophrenia among Han Chinese.

[Effects of Different Altitudes on Soil Microbial PLFA and Enzyme Activity in Two Kinds of Forests].

The soil microbial community is an important part in soil ecosystem, and it is sensitive to the ecological environment. Phospholipid-derived fatty acids ( PLFA ) analysis was used to examine variations in soil microbial community diversity and its influencing factors. The results showed that: there existed 48 PLFAs that were significant in the soil samples from six altitudes. The PLFAs of six altitudes with the highest contents were i16:0, 10Me17:0, 10Me18:0 TBSA. The citrus forest exhibited richer soil PLFAs distribution both in type and amount than those in masson pine. The microbial activity and functional diversity of masson pine were increased with increasing altitudes, and citrus forest gradually decreased, the PLFA content of different microbial groups in each altitude were significantly different. The richness index, Shannon-Wiener index and Pielou evenness index of masson pine in low elevation were holistically higher than those in high elevation. However, the highest richness index of citrus forest was in low altitude, the highest Shannon-Wiener index and Pielou evenness index were in high altitude. The PLFAs content of different microbial groups were closely correlated to the soil enzyme activities and environmental factors. The PLFAs of bacteria, actinomycetes, G⁻ (Gram- positive), G⁺ (Gram-negative) were positively correlated with Ure(urease) , Ive(invertase) , CAT( catalase activity) and forest type, the PLFAs of fungi was significantly correlated with Ure, Ive, CAT, the PLFAs of bacteria, fungi, actinomycetes, G⁻ , G⁺ were significantly negatively or less correlated with elevation. Ure, Ive, CAT, forest type and elevation are the pivotal factors controlling the soil microbial biomass and activities.