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The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.
Methods
By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.
Results
SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07–1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06–1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04–1.18, p = 1.84 × 10−3).
Conclusions
We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.
Radio frequency (RF) breakdown can result in pulse shortening and seriously degrade the stability and reliability of relativistic backward wave oscillators (RBWOs). This paper discusses the energy range of electrons causing breakdown traces in slow-wave structures (SWSs) through particle-in-cell (PIC) simulation, numerical calculation, and experimental verification. The PIC simulation and numerical calculation results reveal that the energy of the majority of the field-induced electrons bombarding the SWS surfaces after being accelerated is less than 120 keV. Furthermore, the micro appearances of the breakdown traces in SWSs and the witness targets bombarded directly by electrons of various energy levels have been analyzed. Scanning electron microscope (SEM) shows that the breakdown traces are featured with corrugated morphologies with a wide range and a shallow depth. A mass of craters emerge in the vicinity of the corrugated morphologies. These appearances are quite similar to destructive traces impacted directly by low-energy electrons (around 160 keV). Thus, it is confirmed that the breakdown traces result from the bombardment of low-energy electrons. Therefore, the breakdown mechanism of field-emitted electrons impacting on the structure surfaces in RBWOs has been further improved.
Aging plays a crucial role in the mechanisms of the impacts of genetic and environmental factors on blood pressure and serum lipids. However, to our knowledge, how the influence of genetic and environmental factors on the correlation between blood pressure and serum lipids changes with age remains to be determined. In this study, data from the Chinese National Twin Registry (CNTR) were used. Resting blood pressure, including systolic and diastolic blood pressure (SBP and DBP), and fasting serum lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) were measured in 2378 participants (1189 twin pairs). Univariate and bivariate structural equation models examined the genetic and environmental influences on blood pressure and serum lipids among three age groups. All phenotypes showed moderate to high heritability (0.37–0.59) and moderate unique environmental variance (0.30–0.44). The heritability of all phenotypes showed a decreasing trend with age. Among all phenotypes, SBP and DBP showed a significant monotonic decreasing trend. For phenotype-phenotype pairs, the phenotypic correlation (Rph) of each pair ranged from −0.04 to 0.23, and the additive genetic correlation (Ra) ranged from 0.00 to 0.36. For TC&SBP, TC&DBP, TG&SBP and TGs&DBP, both the Rph and Ra declined with age, and the Ra difference between the young group and the older adult group is statistically significant (p < .05). The unique environmental correlation (Re) of each pair did not follow any pattern with age and remained relatively stable with age. In summary, we observed that the heritability of blood pressure was affected by age. Moreover, blood pressure and serum lipids shared common genetic backgrounds, and age had an impact on the phenotypic correlation and genetic correlations.
It is crucial to understand the genetic mechanisms and biological pathways underlying the relationship between obesity and serum lipid levels. Structural equation models (SEMs) were constructed to calculate heritability for body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the genetic connections between BMI and the four classes of lipids using 1197 pairs of twins from the Chinese National Twin Registry (CNTR). Bivariate genomewide association studies (GWAS) were performed to identify genetic variants associated with BMI and lipids using the records of 457 individuals, and the results were further validated in 289 individuals. The genetic background affecting BMI may differ by gender, and the heritability of males and females was 71% (95% CI [.66, .75]) and 39% (95% CI [.15, .71]) respectively. BMI was positively correlated with TC, TG and LDL-C in phenotypic and genetic correlation, while negatively correlated with HDL-C. There were gender differences in the correlation between BMI and lipids. Bivariate GWAS analysis and validation stage found 7 genes (LOC105378740, LINC02506, CSMD1, MELK, FAM81A, ERAL1 and MIR144) that were possibly related to BMI and lipid levels. The significant biological pathways were the regulation of cholesterol reverse transport and the regulation of high-density lipoprotein particle clearance (p < .001). BMI and blood lipid levels were affected by genetic factors, and they were genetically correlated. There might be gender differences in their genetic correlation. Bivariate GWAS analysis found MIR144 gene and its related biological pathways may influence obesity and lipid levels.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
Aims
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
Method
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
Results
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
Conclusions
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
The objective of this study was to investigate how different obesity measures link to circulating metabolites, and whether the connections are due to genetic or environmental factors. A cross-sectional analysis was performed on follow-up survey data at the Chinese National Twin Registry (CNTR), which was conducted in four areas of China (Shandong, Jiangsu, Zhejiang and Sichuan) in 2013. The survey collected detailed questionnaire information and conducted physical examinations, fasting blood sampling and untargeted metabolomic measurements among 439 adult twins. Linear regression models and bioinformatics analysis were used to examine the relation of obesity measures, including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with serum metabolite levels and related pathways. A co-twin control study was additionally conducted among 15 obesity-discordant monozygotic (MZ) pairs (intrapair BMI difference >3 kg/m2) to examine any differences in metabolites controlling for genetic factors. Eleven metabolites were associated with BMI, WC and WHR after controlling for genetic and shared environmental factors. Pathway analysis identified pathways such as phenylalanine metabolism, purine metabolism, valine, leucine and isoleucine biosynthesis that were associated with obesity. A wide range of unfavorable alterations in the serum metabolome was associated with obesity. Obesity-discordant twin analysis suggests that these associations are independent of genetic liability.
Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.
Terrorist attacks can occur anywhere. As the threat of terrorism develops, the China-Eurasia Expo held in Ürümqi, China is attracting fewer potential visitors. A nationwide survey of 2034 residents from 31 provinces and municipalities in China was conducted to examine the relation between the distance to respondents’ city of residence from Ürümqi and their levels of concern for safety and security concerning the Expo. The two were found to be positively related: the closer the respondents lived to Ürümqi, the less concerned they were with the safety and security of the Expo. This is consistent with the “psychological typhoon eye” effect, which states that people living closer to the center of an unfortunate event (whether natural or man-made hazards) are less concerned with the event’s negative consequences. This effect appears to hold for terrorism. There are implications of this finding for international counter-terrorism practice, tourism, and research.
The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
Aims
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Method
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
Results
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
Conclusions
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
Nutrition therapy is considered an important treatment of burn patients. The aim of the study was to delineate the nutritional support in severe burn patients and to investigate association between nutritional practice and clinical outcomes. Severe burn patients were enrolled (n 100). In 90 % of the cases, the burn injury covered above 70 % of the total body surface area. Mean interval from injury to nutrition start was 2·4 (sd 1·1) d. Sixty-seven patients were initiated with enteral nutrition (EN) with a median time of 1 d from injury to first feed. Twenty-two patients began with parenteral nutrition (PN). During the study, thirty-two patients developed EN intolerance. Patients received an average of about 70 % of prescribed energy and protein. Patients with EN providing <30 % energy had significantly higher 28- d and in-hospital mortality than patients with EN providing more than 30 % of energy. Mortality at 28 d was 11 % and in-hospital mortality was 45 %. Multiple regression analysis demonstrated that EN providing <30 % energy and septic shock were independent risk factors for 28- d prognosis. EN could be initiated early in severe burn patients. Majority patients needed PN supplementation for energy requirement and EN feeding intolerance. Post-pyloric feeding is more efficient than gastric feeding in EN tolerance and energy supplement. It is difficult for severe burn patients to obtain enough feeding, especially in the early stage of the disease. More than 2 weeks of underfeeding is harmful to recovery.
Chickenpox is a common acute and highly contagious disease in childhood; moreover, there is currently no targeted treatment. Carrying out an early warning on chickenpox plays an important role in taking targeted measures in advance as well as preventing the outbreak of the disease. In recent years, the infectious disease dynamic model has been widely used in the research of various infectious diseases. The logistic differential equation model can well demonstrate the epidemic characteristics of epidemic outbreaks, gives the point at which the early epidemic rate changes from slow to fast. Therefore, our study aims to use the logistic differential equation model to explore the epidemic characteristics and early-warning time of varicella. Meanwhile, the data of varicella cases were collected from first week of 2008 to 52nd week of 2017 in Changsha. Finally, our study found that the logistic model can be well fitted with varicella data, besides the model illustrated that there are two peaks of varicella at each year in Changsha City. One is the peak in summer–autumn corresponding to the 8th–38th week; the other is in winter–spring corresponding to the time from the 38th to the seventh week next year. The ‘epidemic acceleration week’ average value of summer–autumn and winter–spring are about the 16th week (ranging from the 15th to 17th week) and 45th week (ranging from the 44th to 47th week), respectively. What is more, taking warning measures during the acceleration week, the preventive effect will be delayed; thus, we recommend intervene during recommended warning weeks which are the 15th and 44th weeks instead.
The prevalence of overweight and obesity is growing rapidly in many countries. Socioeconomic inequalities might be important for this increase. The aim of this study was to determine associations of body mass index (BMI), overweight and obesity with educational level and marital status in Chinese twins. Participants were adult twins recruited through the Chinese National Twin Registry (CNTR), aged 18 to 79 years, and the sample comprised 10,448 same-sex twin pairs. Current height, weight, educational attainment, and marital status were self-reported. Regression analyses and structural equation models were conducted to evaluate BMI, overweight, and obesity associated with educational level and marital status in both sexes. At an individual level, both educational level and marital status were associated with higher BMI and higher risk of being overweight and obesity in men, while in women the effects of educational level on BMI were in the opposite direction. In within-Monozygotic (MZ) twin-pair analyses, the effects of educational level on BMI disappeared in females. Bivariate structural equation models showed that genetic factors and shared environmental confounded the relationship between education and BMI in females, whereas marital status was associated with BMI on account of significant positive unique environmental correlation apart in both sexes. The present data suggested that marital status and BMI were associated, independent of familiar factors, for both sexes of this study population, while common genetic and shared environmental factors contributed to education-associated disparities in BMI in females.
Obesity is associated with blood pressure (BP), but the associations between different obesity indicators and BP have not reached agreement. Besides, both obesity and BP are influenced by genetic and environmental factors. Whether they share the same genetic or environmental etiology has not been fully understood. We therefore analyzed the relationship between different obesity indicators and BP components as well as the genetic and environmental contributions to these relationships in a Chinese adult twin sample. Twins aged 18–79 years (n = 941) were included in this study. Body mass index (BMI) was used as the index of general obesity, whereas waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) were used as the indicators of central obesity. BP components included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Linear regression models and bivariate structural equation models were used to examine the relation of various obesity indicators with BP components, and genetic or environmental influences on these associations, respectively. A strong association of BP components with BMI—and a somewhat weaker association with WC, WHtR, and WHR—was found in both sexes, independent of familial factors. Of these phenotypic correlations between obesity indicators and BP components, 60–76% were attributed to genetic factors, whereas 24–40% were attributed to unique environmental factors. General obesity was most strongly associated with high BP in Chinese adult twins. There were common genetic backgrounds for obesity and BP, and unique environmental factors also played a role.
This study examined the genetic and environmental effects on variances in weight, height, and body mass index (BMI) under 18 years in a population-based sample from China. We selected 6,644 monozygotic and 5,969 dizygotic twin pairs from the Chinese National Twin Registry (CNTR) aged under 18 years (n = 12,613). Classic twin analyses with sex limitation were used to estimate the genetic and environmental components of weight, height, and BMI in six age groups. Sex-limitation of genetic and shared environmental effects was observed, especially when puberty begins. Heritability for weight, height, and BMI was low at 0–2 years old (less than 20% for both sexes) but increased over time, accounting for half or more of the variance in the 15–17 year age group for boys. For girls, heritabilities for weight, height and BMI was maintained at approximately 30% after puberty. Common environmental effects on all body measures were high for girls (59–87%) and presented a small peak during puberty. Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in the pre-adolescent period and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. Further studies about puberty-related genes and social environment are needed to clarify the mechanism of sex differences.
Twins reared apart provide a fascinating experiment to distinguish genetic from environmental influences. However, there is as yet no broad report on distribution of twins reared apart, especially in the Chinese population. In this study, information on 18,295 volunteer twin pairs of all age groups was compiled in nine provinces or cities of China, and questionnaires were used for zygosity determination. It was discovered that twins reared apart from 0 to 10 years of age accounted for 2.2% of all twin interviewees, with the proportion of this 0–10 group separated before 1, 2, and 5 years old, accounting for 65.3%, 76.1%, and 91.3%, respectively. The proportion of twins reared apart is not significantly related to zygosity or gender, but it is related to region and twin age. As the age of twins lowers, the proportion of those reared apart gradually decreases. Twins reared apart will become rarer in the future and therefore should be cherished as a resource.
To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors.
Design
The study included cohort participants whose urinary ITC levels had been previously ascertained. Urinary ITC was assessed using HPLC. Usual dietary intake of cruciferous vegetables was assessed using a validated FFQ and total dietary ITC intake was calculated. Recent cruciferous vegetable intake was determined. GST genotypes were assessed using duplex real-time quantitative PCR assays. Spearman correlations were calculated between the covariates and urinary ITC levels and linear regression analyses were used to calculate the mean urinary ITC excretion according to GST genotype.
Setting
Urban city in China.
Subjects
The study included 3589 women and 1015 men from the Shanghai Women’s and Men’s Health Studies.
Results
Median urinary ITC level was 1·61 nmol/mg creatinine. Self-reported usual cruciferous vegetable intake was weakly correlated with urinary ITC level (rs=0·1149; P<0·0001), while self-reported recent intake was more strongly correlated with urinary ITC (rs=0·2591; P<0·0001). Overall, the GST genotypes were not associated with urinary ITC level, but significant differences according to genotype were observed among current smokers and participants who provided an afternoon urine sample. Other factors, including previous gastrectomy or gastritis, were also related to urinary ITC level.
Conclusions
The study suggests that urinary secretion of ITC may provide additional information on cruciferous vegetable intake and that GST genotypes are related to urinary ITC level only in some subgroups.
The high repetition rate 10 J/10 ns Yb:YAG laser system and its key techniques are reported. The amplifiers in this system have a multi-pass V-shape structure and the heat in the amplifiers is removed by means of laminar water flow. In the main amplifier, the laser is four-pass, and an approximately 8.5 J/1 Hz/10 ns output is achieved in the primary test. The far-field of the output beam is approximately 10 times the diffraction limit. Because of the higher levels of amplified spontaneous emission (ASE) in the main amplifier, the output energy is lower than expected. At the end we discuss some measures that can improve the properties of the laser system.
We review the present status and future prospects of fast ignition (FI) research of the theoretical group at the IAPCM (Institute of Applied Physics and Computational Mathematics, Beijing) as a part of the inertial confinement fusion project. Since the approval of the FI project at the IAPCM, we have devoted our efforts to improving the integrated codes for FI and designing advanced targets together with the experimental group. Recent FI experiments [K. U. Akli et al., Phys. Rev. E 86, 065402 (2012)] showed that the petawatt laser beam energy was not efficiently converted into the compressed core because of the beam divergence of relativistic electron beams. The coupling efficiency can be improved in three ways: (1) using a cone–wire-in-shell advanced target to enhance the transport efficiency, (2) using external magnetic fields to collimate fast electrons, and (3) reducing the prepulse level of the petawatt laser beam. The integrated codes for FI, named ICFI, including a radiation hydrodynamic code, a particle-in-cell (PIC) simulation code, and a hybrid fluid–PIC code, have been developed to design this advanced target at the IAPCM. The Shenguang-II upgraded laser facility has been constructed for FI research; it consists of eight beams (in total $24~ {\rm kJ}/3\omega $, 3 ns) for implosion compression, and a heating laser beam (0.5–1 kJ, 3–5 ps) for generating the relativistic electron beam. A fully integrated FI experiment is scheduled for the 2014 project.