Surveillance results of viral diarrhea in children under five years of age in Shaoxing City / 预防医学

Objective@#To investigate the epidemiological and etiological characteristics of viral diarrhea among children under 5 years of age in Shaoxing City, Zhejiang Province, so as to provide insights into management of viral diarrhea.@*Methods@#The surveillance data on viral diarrhea among children under 5 years of age in Shaoxing City from 2019 to 2022 were collected, including demographics and stool testing results. The epidemiological and etiological characteristics of viral diarrhea were analyzed using a descriptive epidemiological method. @*Results@#A total of 763 diarrheal children under 5 years of age were reported in Shaoxing City from 2019 to 2022, and 236 children were tested positive for virus (30.93%). The detection of virus was 49.01%, 31.61%, 20.43% and 21.89% from 2019 to 2022, which appeared an overall tendency towards a decline (P<0.05). The incidence of viral diarrhea peaked from November to March of the next year and from May to July, and the detection of virus was lower among children with diarrhea living in urban areas (Yuecheng District, Keqiao District and Shangyu District) than among those in suburb areas (Zhuji City, Shengzhou City and Xinchang County) (30.22% vs. 52.00%, P<0.05). There were 206 children tested positive for a single virus, and the detection rates of rotavirus (RV), enteric adenovirus (EAdV), norovirus (NoV), and sapovirus (SaV) were 9.57%, 8.91%, 8.39%, and 0.13%, respectively. There were 25 children with virus co-infections, and the positive rates of EAdV and NoV, RV and EAdV and RV and NoV co-infections were 1.31%, 1.18% and 0.79%, respectively. There were 5 children with triple infections of RV, EAdV and NoV (0.66%). The highest detection of EAdV was seen in April, the highest detection of RV and NoV was seen in January, while SaV was only detected in April. @*Conclusion@#The incidence of viral diarrhea among children under 5 years of age peaked in winter and spring in Shaoxing City from 2019 to 2022, and the cases predominantly occurred in urban areas. The detection of virus appeared an overall tendency towards a decline, with high detection of RV, EAdV and NoV.

Epidemiological characteristics of hemorrhagic fever with renal syndrome in Shaoxing City from 2006 to 2022 / 预防医学

Objective@#To investigate the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shaoxing City from 2006 to 2022, so as provide insights into improvements of the HFRS control strategy.@*Methods@#Data pertaining to HFRS cases in Shaoxing City from 2006 to 2022 were captured from the Surveillance System of China Information System for Disease Control and Prevention. The temporal, population and regional distributions of HFRS were analyzed using the descriptive epidemiological method, and the trends in incidence of HFRS were evaluated using annual percent change (APC). @*Results@#Totally 1 022 HFRS cases were reported in Shaoxing City from 2006 to 2022, with annual average incidence of 1.22/105 and three deaths. The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022 (APC=-11.101%, t=-9.930, P<0.001), and the incidence of HFRS peaked from May to June and from November to January of the next year. A higher incidence of HFRS was seen in men than in women (1.76/105 vs. 0.68/105; χ2=201.361, P<0.001). There were 714 HFRS cases at ages of 30 to 59 years (69.86%), and farmers were the predominant occupation (78.18%). The three counties with the largest number of HFRS cases included Zhuji (366 cases), Xinchang (263 cases) and Shengzhou (134 cases). The incidence of HFRS was lower in urban districts (Yuecheng, Keqiao and Shangyu) than in counties (Zhuji, Shengzhou and Xinchang) (0.58/105 vs. 1.96/105; χ2=326.880, P<0.001).@*Conclusion@#The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022, and the incidence was high in late spring, early summer and winter. The HFRS cases were mainly males, young and middle-aged people, and farmers, and predominantly distributed in counties. Targeted control measures are needed.

Assessing Causal Relationship Between Human Blood Metabolites and Five Neurodegenerative Diseases With GWAS Summary Statistics.

Background: Neurodegenerative diseases (NDDs) are the leading cause of disability worldwide while their metabolic pathogenesis is unclear. Genome-wide association studies (GWASs) offer an unprecedented opportunity to untangle the relationship between metabolites and NDDs. Methods: By leveraging two-sample Mendelian randomization (MR) approaches and relying on GWASs summary statistics, we here explore the causal association between 486 metabolites and five NDDs including Alzheimer's Disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson's disease (PD), and multiple sclerosis (MS). We validated our MR results with extensive sensitive analyses including MR-PRESSO and MR-Egger regression. We also performed linkage disequilibrium score regression (LDSC) and colocalization analyses to distinguish causal metabolite-NDD associations from genetic correlation and LD confounding of shared causal genetic variants. Finally, a metabolic pathway analysis was further conducted to identify potential metabolite pathways. Results: We detected 164 metabolites which were suggestively associated with the risk of NDDs. Particularly, 2-methoxyacetaminophen sulfate substantially affected ALS (OR = 0.971, 95%CIs: 0.961 ∼ 0.982, FDR = 1.04E-4) and FTD (OR = 0.924, 95%CIs: 0.885 ∼ 0.964, FDR = 0.048), and X-11529 (OR = 1.604, 95%CIs: 1.250 ∼ 2.059, FDR = 0.048) and X-13429 (OR = 2.284, 95%CIs: 1.457 ∼ 3.581, FDR = 0.048) significantly impacted FTD. These associations were further confirmed by the weighted median and maximum likelihood methods, with MR-PRESSO and the MR-Egger regression removing the possibility of pleiotropy. We also observed that ALS or FTD can alter the metabolite levels, including ALS and FTD on 2-methoxyacetaminophen sulfate. The LDSC and colocalization analyses showed that none of the identified associations could be driven by genetic correlation or confounding by LD with common causal loci. Multiple metabolic pathways were found to be involved in NDDs, such as "urea cycle" (P = 0.036), "arginine biosynthesis" (P = 0.004) on AD and "phenylalanine, tyrosine and tryptophan biosynthesis" (P = 0.046) on ALS. Conclusion: our study reveals robust bidirectional causal associations between servaral metabolites and neurodegenerative diseases, and provides a novel insight into metabolic mechanism for pathogenesis and therapeutic strategies of these diseases.

Type 2 Diabetes Mellitus and Amyotrophic Lateral Sclerosis: Genetic Overlap, Causality, and Mediation.

CONTEXT: Understanding phenotypic connection between type II diabetes (T2D) mellitus and amyotrophic lateral sclerosis (ALS) can offer valuable sight into shared disease etiology and have important implication in drug repositioning and therapeutic intervention. OBJECTIVE: This work aims to disentangle the nature of the inverse relationship between T2D mellitus and ALS. METHODS: Depending on summary statistics of T2D (n = 898 130) and ALS (n = 80 610), we estimated the genetic correlation between them and prioritized pleiotropic genes through a multiple-tissue expression quantitative trait loci-weighted integrative analysis and the conjunction conditional false discovery rate (ccFDR) method. We implemented mendelian randomization (MR) analyses to evaluate the causal relationship between the 2 diseases. A mediation analysis was performed to assess the mediating role of T2D in the pathway from T2D-related glycemic/anthropometric traits to ALS. RESULTS: We found supportive evidence of a common genetic foundation between T2D and ALS (rg = -0.223, P = .004) and identified 8 pleiotropic genes (ccFDR < 0.10). The MR analyses confirmed that T2D exhibited a neuroprotective effect on ALS, leading to an approximately 5% (95% CI, 0% ~ 9.6%, P = .038) reduction in disease risk. In contrast, no substantial evidence was observed that supported the causal influence of ALS on T2D. The mediation analysis revealed T2D can also serve as an active mediator for several glycemic/anthropometric traits, including high-density lipoprotein cholesterol, overweight, body mass index, obesity class 1, and obesity class 2, with the mediation effect estimated to be 0.024, -0.022, -0.041, -0.016, and -0.012, respectively. CONCLUSION: We provide new evidence supporting the observed inverse link between T2D and ALS, and revealed that a shared genetic component and causal association commonly drove such a relationship. We also demonstrate the mediating role of T2D standing in the pathway from T2D-related glycemic/anthropometric traits to ALS.

New novel non-MHC genes were identified for cervical cancer with an integrative analysis approach of transcriptome-wide association study.

Although genome-wide association studies (GWAS) have successfully identified multiple genetic variants associated with cervical cancer, the functional role of those variants is not well understood. To bridge such gap, we integrated the largest cervical cancer GWAS (N = 9,347) with gene expression measured in six human tissues to perform a multi-tissue transcriptome-wide association study (TWAS). We identified a total of 20 associated genes in the European population, especially four novel non-MHC genes (i.e. WDR19, RP11-384K6.2, RP11-384K6.6 and ITSN1). Further, we attempted to validate our results in another independent cervical cancer GWAS from the East Asian population (N = 3,314) and re-discovered four genes including WDR19, HLA-DOB, MICB and OR2B8P. In our subsequent co-expression analysis, we discovered SLAMF7 and LTA were co-expressed in TCGA tumor samples and showed both WDR19 and ITSN1 were enriched in "plasma membrane". Using the protein-protein interaction analysis we observed strong interactions between the proteins produced by genes that are associated with cervical cancer. Overall, our study identified multiple candidate genes, especially four non-MHC genes, which may be causally associated with the risk of cervical cancer. However, further investigations with larger sample size are warranted to validate our findings in diverse populations.

Improved Detection of Potentially Pleiotropic Genes in Coronary Artery Disease and Chronic Kidney Disease Using GWAS Summary Statistics.

The coexistence of coronary artery disease (CAD) and chronic kidney disease (CKD) implies overlapped genetic foundation. However, the common genetic determination between the two diseases remains largely unknown. Relying on summary statistics publicly available from large scale genome-wide association studies (n = 184,305 for CAD and n = 567,460 for CKD), we observed significant positive genetic correlation between CAD and CKD (r g = 0.173, p = 0.024) via the linkage disequilibrium score regression. Next, we implemented gene-based association analysis for each disease through MAGMA (Multi-marker Analysis of GenoMic Annotation) and detected 763 and 827 genes associated with CAD or CKD (FDR < 0.05). Among those 72 genes were shared between the two diseases. Furthermore, by integrating the overlapped genetic information between CAD and CKD, we implemented two pleiotropy-informed informatics approaches including cFDR (conditional false discovery rate) and GPA (Genetic analysis incorporating Pleiotropy and Annotation), and identified 169 and 504 shared genes (FDR < 0.05), of which 121 genes were simultaneously discovered by cFDR and GPA. Importantly, we found 11 potentially new pleiotropic genes related to both CAD and CKD (i.e., ARHGEF19, RSG1, NDST2, CAMK2G, VCL, LRP10, RBM23, USP10, WNT9B, GOSR2, and RPRML). Five of the newly identified pleiotropic genes were further repeated via an additional dataset CAD available from UK Biobank. Our functional enrichment analysis showed that those pleiotropic genes were enriched in diverse relevant pathway processes including quaternary ammonium group transmembrane transporter, dopamine transport. Overall, this study identifies common genetic architectures overlapped between CAD and CKD and will help to advance understanding of the molecular mechanisms underlying the comorbidity of the two diseases.

Relationship between birth weight and chronic kidney disease: evidence from systematics review and two-sample Mendelian randomization analysis.

Observational studies showed an inverse association between birth weight and chronic kidney disease (CKD) in adulthood existed. However, whether such an association is causal remains fully elusive. Moreover, none of prior studies distinguished the direct fetal effect from the indirect maternal effect. Herein, we aimed to investigate the causal relationship between birth weight and CKD and to understand the relative fetal and maternal contributions. Meta-analysis (n = ~22 million) showed that low birth weight led to ~83% (95% confidence interval [CI] 37-146%) higher risk of CKD in late life. With summary statistics from large scale GWASs (n = ~300 000 for birth weight and ~481 000 for CKD), linkage disequilibrium score regression demonstrated birth weight had a negative maternal, but not fetal, genetic correlation with CKD and several other kidney-function related phenotypes. Furthermore, with multiple instruments of birth weight, Mendelian randomization showed there existed a negative fetal casual association (OR = 1.10, 95% CI 1.01-1.16) between birth weight and CKD; a negative but non-significant maternal casual association (OR = 1.09, 95% CI 0.98-1.21) was also identified. Those associations were robust against various sensitivity analyses. However, no maternal/fetal casual effects of birth weight were significant for other kidney-function related phenotypes. Overall, our study confirmed the inverse association between birth weight and CKD observed in prior studies, and further revealed the shared maternal genetic foundation between low birth weight and CKD, and the direct fetal and indirect maternal causal effects of birth weight may commonly drive this negative relationship.

Potential Genes Associated with the Survival of Lung Adenocarcinoma Were Identified by Methylation.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. The purpose of this study is to search for genes related to the prognosis of LUAD through methylation based on a linear mixed model (LMM). METHODS: Gene expression, methylation, and survival data of LUAD patients were downloaded from the TCGA database. Based on the LMM model, the GEMMA algorithm was used to screen the predictive genes related to LUAD survival. The Cox model was used to further screen the predicted genes, and then, protein-protein interaction (PPI) network was constructed. Through the software plugin Cytoscape MCODE 3.8.0, the most closely related genes in the PPI network module were selected for in-depth biological function analysis to further explore the interaction and correlation between genes. RESULTS: We screened out 97 predictive genes from 18,834 genes and eliminated one gene associated with lung squamous cell carcinoma from previous studies, leaving 96 genes. The MCODE and the Kaplan-Meier curve analysis were used to finally identify two genes ASB16 and NEDD4 that are related to the prognosis of LUAD. CONCLUSIONS: The newly identified two genes associated with the prognosis of LUAD may provide a basis for the treatment of patients.

Are blood lipids risk factors for fracture? Integrative evidence from instrumental variable causal inference and mediation analysis using genetic data.

BACKGROUND: The relationship between lipids and the risk of fracture is currently controversial and whether such association is causal remains elusive. METHODS: We performed two-sample inverse variance weighted (IVW) Mendelian randomization (MR) analyses to evaluate causal effects of four lipids (i.e. high-density lipoprotein cholesterol [HDL], low-density lipoprotein cholesterol [LDL], total cholesterol [TC] and triglyceride [TG]) on fracture or bone mineral density (BMD) with summary statistics from large scale genome-wide association studies (up to ~190,000 for lipids, ~66,628 for BMD and ~53,000 for fracture). We validated our MR results with extensive sensitive analyses including MR-PRESSO and MR-Egger regression. Multivariable analyses were implemented to investigate whether other lipids (i.e. LDL and TG) may confound the causal effect of HDL on fracture and mediation analyses were conducted to assess indirect effects of lipids on fracture mediated by BMD. RESULTS: The IVW MR showed there existed a statistically significant association between HDL and fracture, with the odd ratio (OR) per standard deviation change of HDL on fracture being 1.12 (95% CI: 1.02-1.22, p = 1.20E-02). HDL was also detected to be causally associated with BMD (beta = -0.116; 95% CI: -0.182 ~ -0.050, p = 5.47E-04). These associations were further confirmed by the weighted median and maximum likelihood methods, with the MR-Egger regression removing the possibility of pleiotropy and the multivariable analysis excluding the confounding effect of other lipids on HDL. Negative associations of HDL with BMD among the elderly and with BMD at the lumbar spine were also discovered. However, no causal associations were detected between other lipids (OR = 0.87, 95% CI: 0.74-1.03, p = .107 for LDL; OR = 1.03; 95% CI: 0.88-1.21, p = .696 for TC and OR = 1.04; 95% CI: 0.90-1.20, p = .610 for TG) and fracture; whereas TG was positively associated BMD (beta = 0.184; 95% CI: 0.048-0.319, p = 7.93E-03). Finally, the mediation effect of BMD was estimated to be -0.116 (95% CI: -0.182 to -0.05, p = 5.47E-04) for HDL or 0.184 (95% CI: 0.048-0.319, p = 7.93E-03) for TG, implying HDL and TG could be indirectly associated with fracture risk via the pathway of BMD. CONCLUSION: Our study is supportive of the causal relationship between HDL and fracture but offers little direct evidence for causal associations between other lipids and fracture, and further reveals HDL and TG may have an indirect influence on fracture mediated by BMD.