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1.
Artigo em Inglês | MEDLINE | ID: mdl-36833784

RESUMO

In order to reduce the content of Cr(VI) in the soil of the relocated chromium salt factory, the rice straw-derived hydrothermal carbon was prepared by hydrothermal method and loaded with nano zero-valent iron generated by liquid phase reduction, which effectively alleviated the self-aggregation problem of nano zero-valent iron (nZVI) in the treatment of Cr(VI) and improved the Cr(VI) reduction rate without changing the soil structure. The reduction effect of Cr(VI) in soil by key influencing factors such as carbon-iron ratio, initial pH value, and initial temperature was investigated. The results showed that nZVI modified hydro-thermal carbon composite (named RC-nZVI) had a good reduction effect on Cr(VI). Scanning electron microscope (SEM) and energy spectrum analysis showed that nZVI was evenly distributed on the surface of hydrothermal carbon, which effectively reduced the agglomeration of iron. Under the conditions of C/Fe = 1:2, 60 °C, with pH of 2, the average Cr(VI) content in soil decreased from 182.9 mg kg-1 to 21.6 mg kg-1. Adsorption kinetics of Cr(VI) by RC-nZVI fit well with the pseudo-second-order model, and the kinetic velocity constant revealed that Cr(VI) reduction rate decreased with increasing initial Cr(VI) concentration. Cr(VI) reduction by RC-nZVI was mainly dominated by chemical adsorption.


Assuntos
Oryza , Poluentes Químicos da Água , Carbono , Ferro/química , Solo/química , Poluentes Químicos da Água/análise , Cromo/análise , Adsorção
2.
Nat Commun ; 13(1): 2939, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35618720

RESUMO

We initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing (WGS) individuals and 5,841 high-density genotyping individuals, and identify 81.5 million SNPs and INDELs, of which 38.5% are absent in dbSNP Build 151. We provide a population-specific reference panel and an online imputation server ( https://wbbc.westlake.edu.cn/ ) which could yield substantial improvement of imputation performance in Chinese population, especially for low-frequency and rare variants. By analyzing the singleton density of the WGS data, we find selection signatures in SNX29, DNAH1 and WDR1 genes, and the derived alleles of the alcohol metabolism genes (ADH1A and ADH1B) emerge around 7,000 years ago and tend to be more common from 4,000 years ago in East Asia. Genetic evidence supports the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains, which separate the Han Chinese into subgroups, and we reveal that North Han was more homogeneous than South Han.


Assuntos
Povo Asiático , Bancos de Espécimes Biológicos , Povo Asiático/genética , China , Genômica , Humanos , Projetos Piloto
3.
Hum Mol Genet ; 30(22): 2177-2189, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34230965

RESUMO

Bone mineral density (BMD) is a highly heritable complex trait and is a key indicator for diagnosis and treatment for osteoporosis. In the last decade, numerous susceptibility loci for BMD and fracture have been identified by genome-wide association studies (GWAS); however, fine mapping of these loci is challengeable. Here, we proposed a new long-range fine-mapping approach that combined superenhancers (SEs) and microRNAs (miRNAs) data, which were two important factors in control of cell identity and specific differentiation, with the GWAS summary datasets in cell-type-restricted way. Genome-wide SE-based analysis found that the BMD-related variants were significantly enriched in the osteoblast SE regions, indicative of potential long-range effects of such SNPs. With the SNP-mapped SEs (mSEs), 13 accessible long-range mSE-interacted miRNAs (mSE-miRNAs) were identified by integrating osteoblast Hi-C and ATAC-seq data, including three known bone-related miRNAs (miR-132-3p, miR-212-3p and miR-125b-5p). The putative targets of the two newly identified mSE-miRNAs (miR-548aj-3p and miR-190a-3p) were found largely enriched in osteogenic-related pathway and processes, suggesting that these mSE-miRNAs could be functional in the regulation of osteoblast differentiation. Furthermore, we identified 54 genes with the long-range 'mSE-miRNA' approach, and 24 of them were previously reported to be related to skeletal development. Besides, enrichment analysis found that these genes were specifically enriched in the post-transcriptional regulation and bone formation processes. This study provided a new insight into the approach of fine-mapping of GWAS loci. A tool was provided for the genome-wide SE-based analysis and the detection of long-range osteoblast-restricted mSE-miRNAs (https://github.com/Zheng-Lab-Westlake/Osteo-Fine-Mapp-SNP2SE2miRNA).


Assuntos
Densidade Óssea/genética , Elementos Facilitadores Genéticos , Epigenômica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genômica , MicroRNAs/genética , Biologia Computacional , Epigenômica/métodos , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Osteoblastos/metabolismo , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas
4.
BMJ Open ; 11(6): e045564, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183340

RESUMO

PURPOSE: The Westlake BioBank for Chinese (WBBC) pilot cohort is a population-based prospective study with its major purpose to better understand the effect of genetic and environmental factors on growth and development from adolescents to adults. PARTICIPANTS: A total of 14 726 participants (4751 males and 9975 females) aged 14-25 years were recruited and the baseline survey was carried out from 2017 to 2019. The pilot cohort contains rich range of information regarding of demographics and anthropometric measurements, lifestyle and sleep patterns, clinical and health outcomes. Visit the WBBC website for more information (https://wbbc.westlake.edu.cn/index.html). FINDINGS TO DATE: The mean age of the study samples were 18.6 years for males and 18.5 years for females, respectively. The mean height and weight were 172.9 cm and 65.81 kg for males, and 160.1 cm and 52.85 kg for females. Results indicated that the prevalence of underweight in female was much higher than male, but the prevalence of overweight and obesity in female was lower than male. The mean serum 25(OH)D level in the 14 726 young participants was 22.4±5.3 ng/mL, and male had a higher level of serum 25(OH)D than female, overall, 33.5% of the participants had vitamin D deficiency and even more participants suffered from vitamin D insufficiency (58.2%). The proportion of deficiency in females was much higher than that in males (41.8 vs 16.4%). The issue of underweight and vitamin D deficiency in young people should be paid attention, especially in females. These results reflected the fact that thinness and paler skin are preferred in modern aesthetics of Chinese culture. FUTURE PLANS: WBBC pilot is designed as a prospective cohort study and provides a unique and rich data set analysing health trajectories from adolescents to young adults. WBBC will continue to collect samples with old age.


Assuntos
Bancos de Espécimes Biológicos , Deficiência de Vitamina D , Adolescente , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Projetos Piloto , Prevalência , Estudos Prospectivos , Vitamina D , Adulto Jovem
5.
Bone Res ; 9(1): 23, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927194

RESUMO

Osteoporosis is a common skeletal disease, affecting ~200 million people around the world. As a complex disease, osteoporosis is influenced by many factors, including diet (e.g. calcium and protein intake), physical activity, endocrine status, coexisting diseases and genetic factors. In this review, we first summarize the discovery from genome-wide association studies (GWASs) in the bone field in the last 12 years. To date, GWASs and meta-analyses have discovered hundreds of loci that are associated with bone mineral density (BMD), osteoporosis, and osteoporotic fractures. However, the GWAS approach has sometimes been criticized because of the small effect size of the discovered variants and the mystery of missing heritability, these two questions could be partially explained by the newly raised conceptual models, such as omnigenic model and natural selection. Finally, we introduce the clinical use of GWAS findings in the bone field, such as the identification of causal clinical risk factors, the development of drug targets and disease prediction. Despite the fruitful GWAS discoveries in the bone field, most of these GWAS participants were of European descent, and more genetic studies should be carried out in other ethnic populations to benefit disease prediction in the corresponding population.

6.
Ann Rheum Dis ; 79(11): 1460-1467, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32737104

RESUMO

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.


Assuntos
Antirreumáticos/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Osteoporose/epidemiologia , Psoríase/complicações , Psoríase/tratamento farmacológico , Humanos , Análise da Randomização Mendeliana
7.
Bone ; 133: 115247, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31968281

RESUMO

Bone mineral density (BMD) is a key indicator for diagnosis and treatment for osteoporosis; the reduction of BMD could increase the risk of osteoporotic fracture. It was very recently found that Piezo1 mediated mechanically evoked responses in bone and further participated in bone formation in mice. Here, we performed cross phenotype meta-analysis for human BMD at lumbar spine (LS), femoral neck (FN), distal radius/forearm (FA) and heel and screened out 14 top SNPs for PIEZO1, these SNPs were overlapped with putative enhancers, DNase-I hypersensitive sites and active promoter flanking regions. We found that the signal of the best SNP rs62048221 was mainly from heel ultrasound estimated BMD (-0.02 SD per T allele, P = 8.50E-09), where calcaneus supported most of the mechanical force of body when standing, walking and doing physical exercises. Each copy of the effect allele T of SNP rs62048221 was associated with a decrease of 0.0035 g/cm2 BMD (P = 4.6E-27, SE = 0.0003) in UK Biobank data within 477,760 samples. SNP rs62048221 was located at the enhancer region (HEDD enhancer ID 2331049) of gene PIEZO1, site-directed ChIP assays in human mesenchymal stem cells (hMSCs) showed significant enrichment of H3K4me1 and H3K27ac in this region, luciferase assays showed that rs62048221 could significantly affect the activity of the enhancer where it resides. Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD.


Assuntos
Osteoporose , Fraturas por Osteoporose , Animais , Densidade Óssea/genética , Colo do Fêmur , Humanos , Canais Iônicos , Vértebras Lombares , Camundongos , Polimorfismo de Nucleotídeo Único/genética
8.
Lipids Health Dis ; 18(1): 74, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922395

RESUMO

BACKGROUND: CD14 polymorphisms are associated with an increased risk of cardiovascular events. So far, many studies have been conducted, whereas the results were not always consistent. MATERIALS AND METHODS: Twenty-six articles involving thirty-seven datasets were recruited to evaluate the association between rs2569190 (9413 patients and 7337 controls), C-159T (4813 patients and 2852 controls) polymorphisms and cardiovascular diseases in a meta-analysis. The random or fixed effect models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals. RESULTS: The strongest association was observed between rs2569190 and CVD in overall population (T vs. C, OR = 1.169, 95% CI: 1.087-1.257, p = 2.44 × 10- 5). Analysis after stratification by ethnicity indicated that rs2569190 was related to CVD in East Asian population (T vs. C, OR = 1.370, 95% CI; 1.226-1.531, p = 2.86 × 10- 8) and a potential relationship in European (T vs. C, OR = 1.100, 95% CI: 1.019-1.189, p = 0.015). In the stratification of endpoints, the associations were found in CHD subgroup (T vs. C, OR = 1.357, 95% CI: 1.157-1.592, p = 2.47 × 10- 7) and in AMI subgroup (T vs. C, OR = 1.152, 95% CI: 1.036-1.281, p = 0.009). However, we did not find any association between C-159T polymorphism with cardiovascular disease under any model. CONCLUSIONS: The SNP rs2569190 significantly contribute to susceptibility and development of cardiovascular disease, particularly in the East Asian population and in the subtype CHD group, in addition, a potential association was observed in the AMI group, T allele acts as a risk factor for cardiovascular disease.


Assuntos
Doenças Cardiovasculares/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Receptores de Lipopolissacarídeos/genética , Alelos , Povo Asiático/genética , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genética
9.
Brief Bioinform ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-32002535

RESUMO

Here, 622 imputations were conducted with 394 customized reference panels for Han Chinese and European populations. Besides validating the fact that imputation accuracy could always benefit from the increased panel size when the reference panel was population specific, the results brought two new thoughts. First, when the haplotype size of the reference panel was fixed, the imputation accuracy of common and low-frequency variants (Minor Allele Frequency (MAF) > 0.5%) decreased while the population diversity of the reference panel increased, but for rare variants (MAF < 0.5%), a small fraction of diversity in panel could improve imputation accuracy. Second, when the haplotype size of the reference panel was increased with extra population-diverse samples, the imputation accuracy of common variants (MAF > 5%) for the European population could always benefit from the expanding sample size. However, for the Han Chinese population, the accuracy of all imputed variants reached the highest when reference panel contained a fraction of an extra diverse sample (8-21%). In addition, we evaluated the imputation performances in the existing reference panels, such as the Haplotype Reference Consortium (HRC), 1000 Genomes Project Phase 3 and the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE). For the European population, the HRC panel showed the best performance in our analysis. For the Han Chinese population, we proposed an optimum imputation reference panel constituent ratio if researchers would like to customize their own sequenced reference panel, but a high-quality and large-scale Chinese reference panel was still needed. Our findings could be generalized to the other populations with conservative genome; a tool was provided to investigate other populations of interest (https://github.com/Abyss-bai/reference-panel-reconstruction).

10.
Database (Oxford) ; 20182018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30239683

RESUMO

Autophagy is the natural, regulated, destructive mechanism of the eukaryotes cell that disassembles unnecessary or dysfunctional components. In recent years, the association between autophagy and diseases has attracted more and more attention, but our understanding of the molecular mechanism about the association in the system perspective is limited and ambiguous. Hence, we developed the comprehensive bioinformatics resource Autophagy To Disease (ATD, http://auto2disease.nwsuaflmz.com) to archive autophagy-associated diseases. This resource provides bioinformatics annotation system about genes and chemicals about autophagy and human diseases by extracting results from previous studies with text mining technology. Based on the big data from ATD, we found that some classes of disease tend to be related with autophagy, including respiratory disease, cancer, urogenital disease and digestive system disease. We also found that some classes of autophagy-related diseases have a strong association among each other and constitute modules. Furthermore, we extracted the autophagy-disease-related genes (ADGs) from ATD and provided a novel algorithm Optimized Random Forest with Label model to predict potential ADGs. This bioinformatics annotation system about autophagy and human diseases may provide a basic resource for the further detection of the molecular mechanisms of autophagy pathway to disease.


Assuntos
Autofagia , Biologia Computacional/métodos , Doença , Algoritmos , Autofagia/genética , Mineração de Dados , Bases de Dados como Assunto , Doença/genética , Ontologia Genética , Humanos , Anotação de Sequência Molecular , Estatística como Assunto
11.
Arch Dermatol Res ; 310(9): 711-728, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30171347

RESUMO

Previous studies have reported that genes relating to JAK-STAT pathway (IFIH1, TYK2 and IL-10) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P = 2.56 × 10-11, OR 1.135, 95% CI 1.094-1.179, dominant: P = 1.8 × 10-8, OR 1.203, 95% CI 1.128-1.284, recessive: P = 2.6 × 10-7, OR 1.163, 95% CI 1.098-1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans (P = 5.82 × 10-5, OR 1.434, 95% CI 1.203-1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model (P = 8.05 × 10-3, OR 1.314, 95% CI 1.074-1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model (P = 4.65 × 10-3, OR 2.623, 95% CI 1.346-5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model (P = 1.21 × 10-2, OR 1.375, 95% CI 1.072-1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P = 4.65 × 10-3, OR 1.539, 95% CI 1.142-2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.


Assuntos
Helicase IFIH1 Induzida por Interferon/genética , Interleucina-10/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , TYK2 Quinase/genética , Frequência do Gene , Predisposição Genética para Doença , Humanos , Janus Quinases/fisiologia , Viés de Publicação , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais/fisiologia
12.
Ecotoxicol Environ Saf ; 160: 32-41, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-29783110

RESUMO

The microbiome in artificial lake water and its impact on mercury (Hg) methylation remain largely unknown. We selected the largest artificial lake in southeastern china, Changshou Lake (CSL), which has high background levels of Hg, for our investigation of Hg transformation microorganisms. Five different sections of the water column of CSL were sampled during four seasons. The water samples were subjected to analysis of geochemical parameters, various Hg species and microbiome information. High concentrations of total mercury (THg) were detected in CSL in comparison with those found in natural lakes. Significant differences in microbial community structure and Hg species abundance existed among seasons. High dissolved methyl mercury (DMeHg) formation and high bacterial richness and diversity occurred in the fall. The microbiome was dominated by Proteobacteria, Actinobacteria, Bacteroidetes, Deinococcus-Thermus and many unclassified bacteria. Significant correlations were found between seasonal bacterial communities and Hg levels. Hg methylation was strongly linked to the abundance of Cyanobacteria. Methylators, including Syntrophus, Desulfovibrio and Desulfomonile species, were detected only in samples collected in the fall. The results of enzyme functional analyses revealed that many unknown types of bacteria could also be responsible for Hg transformation. This study was the first to investigate the impact of various Hg species on the microbiome of artificial lake water. The findings of this study illuminate the role of seasonal bacteria in Hg transformation.


Assuntos
Lagos/microbiologia , Compostos de Metilmercúrio/análise , Microbiologia da Água , Poluentes Químicos da Água/análise , Bactérias/isolamento & purificação , Bactérias/metabolismo , China , Monitoramento Ambiental , Lagos/química , Mercúrio/metabolismo , Metilação , Microbiota , Estações do Ano
13.
J Alzheimers Dis ; 61(3): 1077-1088, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29332039

RESUMO

Large-scale genome-wide association studies have reported EPHA1 rs11767557 variant to be associated with Alzheimer's disease (AD) risk in the European population. However, it is still unclear how this variant functionally contributes to the underlying disease pathogenesis. The rs11767557 variant is located approximately 3 kb upstream of EPHA1 gene. We think that rs11767557 may modify the expression of nearby genes such as EPHA1 and further cause AD risk. Until now, the potential association between rs11767557 and the expression of nearby genes has not been reported in previous studies. Here, we evaluate the potential expression association between rs11767557 and EPHA1 using multiple large-scale eQTLs datasets in human brain tissues and the whole blood. The results show that rs11767557 variant could significantly regulate EPHA1 gene expression specifically in human whole blood. These findings may further provide important supplementary information about the regulating mechanisms of rs11767557 variant in AD risk.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Receptor EphA1/sangue , Receptor EphA1/genética , Estudos de Casos e Controles , China , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Medição de Risco
14.
J Environ Manage ; 206: 418-429, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29102844

RESUMO

Dissolved organic matter (DOM) plays an important environmental and ecological role in inland aquatic systems, including lakes. In this study, using fluorescence analysis, we investigated the seasonal dynamics of DOM characteristics in Changshou Lake, which is a typical inland lake in the Three Gorges Reservoir (TGR) area. We also discuss the environmental implications of DOM for mercury (Hg) dynamics. Based on the origins of two end-members, the variations in DOM observed in this study in Changshou Lake suggest that hydrological processes (e.g., terrestrial inputs resulting from runoff and humic-like component residences) and biological activities (e.g., microbial and algae growth) are the two main principal components controlling the seasonal dynamics of DOM characteristics. Furthermore, the dynamics of dissolved Hg co-varied with variations in DOM properties, rather than with dissolved organic carbon (DOC) concentrations. This indicates that the previously reported simple correlations between DOC and Hg were not comprehensive and may lead to misunderstanding the interactions between DOM and Hg. Therefore, we recommend that when using DOM-Hg correlations to evaluate the role of DOM in the environmental fate of Hg, especially in field investigations of the spatial and temporal distribution of Hg, the properties of DOM must be taken into account.


Assuntos
Monitoramento Ambiental , Mercúrio/análise , Carbono , Corantes , Fluorescência , Lagos , Compostos Orgânicos
15.
Neurol Sci ; 38(7): 1255-1262, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28429084

RESUMO

In 2006, a candidate gene study reported death-associated protein kinase 1 (DAPK1) rs4878104 variant to be significantly associated with Alzheimer's disease (AD) risk. However, the following studies showed inconsistent association results. Here, we conducted an updated analysis to investigate the potential association between rs4878104 and AD using a total of 60,751 samples (20,161 AD cases and 40,590 controls). In the pooled population, the results based on the allele and genotype genetic models show that rs4878104 variant is not significantly associated with AD risk. Interestingly, we identified rs4878104 variant to be significantly associated with AD risk in American population and Chinese population in subgroup analysis. Using multiple large-scale expression quantitative trait loci datasets, we further found that rs4878104 T allele could significantly regulate increased DAPK1 expression in European population. These findings suggest that rs4878104 may contribute AD susceptibility by modifying DAPK1 expression in European population.


Assuntos
Doença de Alzheimer/genética , Proteínas Quinases Associadas com Morte Celular/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Proteínas Reguladoras de Apoptose/genética , Povo Asiático/genética , Feminino , Humanos , Masculino , Risco , População Branca/genética
16.
J Neurol Sci ; 375: 18-22, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28320126

RESUMO

A genome-wide association study identified GAB2 rs2373115 to be associated with Alzheimer's disease (AD) risk in European population. However, inconsistent results are reported in East Asian population. Here, we performed an updated analysis using 65,704 samples including 20,982 AD cases and 44,722 controls. First, we investigated the GAB2 rs2373115 variant in Asian population using 3974 AD cases and 7568 controls. To further evaluate the effect of rs2373115 in different populations, we selected 17,008 AD cases and 37,154 controls in European population. We used three genetic models, and found no significant heterogeneity in Asian population. A fixed effect model analysis showed no significant association between rs2373115 and AD in Asian population. There was no significant heterogeneity in the pooled East Asian and European populations. The fixed effect model analysis again showed no significant association between rs2373115 and AD in these pooled populations. Taken together, these findings suggest that GAB2 rs2373115 may contribute to AD susceptibility only in European population but not in East Asian population.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Doença de Alzheimer/epidemiologia , Povo Asiático/genética , Bases de Dados Bibliográficas/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Metanálise como Assunto , População Branca/genética
17.
Brief Bioinform ; 18(1): 98-104, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26851225

RESUMO

Reproductive infertility affects seventh of couples, which is most attributed to the obstacle of gametogenesis. Characterizing the epigenetic modification factors involved in gametogenesis is fundamental to understand the molecular mechanisms and to develop treatments for human infertility. Although the genetic factors have been implicated in gametogenesis, no dedicated bioinformatics resource for gametogenesis is available. To elucidate the relationship of epigenetic modification and mammalian gametogenesis, we developed a new database, gametogenesis epigenetic modification database (GED), a manually curated database, which aims at providing a comprehensive resource of epigenetic modification of gametogenesis. The database integrates three kinds information of epigenetic modifications during gametogenesis (DNA methylation, histone modification and RNA regulation), and the gametogenesis has been detailed as 16 stages in seven mammal species (Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa, Bos taurus, Capra hircus and Ovis aries). Besides, we have predicted the linear pathways of epigenetic modification which were composed of 211 genes/proteins and microRNAs that were involved in gametogenesis. GED is a user-friendly Web site, through which users can obtain the comprehensive epigenetic factor information and molecular pathways by visiting our database freely. GED is free available at http://gametsepi.nwsuaflmz.com.


Assuntos
Epigênese Genética , Animais , Metilação de DNA , Bases de Dados Factuais , Gametogênese , Humanos , MicroRNAs
18.
Brief Bioinform ; 18(4): 712-721, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27373733

RESUMO

Gametogenesis is a complex process, which includes mitosis and meiosis and results in the production of ovum and sperm. The development of gametogenesis is dynamic and needs many different genes to work synergistically, but it is lack of global perspective research about this process. In this study, we detected the dynamic process of gametogenesis from the perspective of systems biology based on protein-protein interaction networks (PPINs) and functional analysis. Results showed that gametogenesis genes have strong synergistic effects in PPINs within and between different phases during the development. Addition to the synergistic effects on molecular networks, gametogenesis genes showed functional consistency within and between different phases, which provides the further evidence about the dynamic process during the development of gametogenesis. At last, we detected and provided the core molecular modules of different phases about gametogenesis. The gametogenesis genes and related modules can be obtained from our Web site Gametogenesis Molecule Online (GMO, http://gametsonline.nwsuaflmz.com/index.php), which is freely accessible. GMO may be helpful for the reference and application of these genes and modules in the future identification of key genes about gametogenesis. Summary, this work provided a computational perspective and frame to the analysis of the gametogenesis dynamics and modularity in both human and mouse.


Assuntos
Gametogênese , Redes Reguladoras de Genes , Animais , Humanos , Meiose , Camundongos , Mapas de Interação de Proteínas , Biologia de Sistemas
19.
Huan Jing Ke Xue ; 37(11): 4168-4178, 2016 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964667

RESUMO

For further understanding the geochemical characteristics of dissolved organic matter (DOM) in "reservoir-type" lake, in this study a typical "reservoir-type" lake, Changshou Lake located in inlands of Three Gorges Reservoir areas, was selected to investigate the composition, sources and spatial distributions of chromophoric DOM (CDOM) in this lake, through UV-Vis and three-dimensional fluorescence spectroscopy combined within analysis of riparian eco-system differences. The results showed that DOM concentrations including dissolved organic carbon (DOC) and CDOM abundance in different sampling sites varied spatially to a certain degree, in contrast to fluorescence component of DOM showing a constant level. In backwater zone (also called stagnant zone alternatively), due to accumulation of DOM and limited impact of terrestrial contribution, the endogenesis (autochthonous production) was the predominant geochemical process showing an obvious "authigenic-control" characteristic, and relatively lower aromaticity and molecular weight. In comparison, sampling sites surrounding artificial forests and tourism development, the highly humic (highly aromatic) substances resulted from terrestrial inputs were the main source, but discharge due to human activities was also responsible for highly protein-like component observed in DOM. Additionally, in the entry zones of lake from upstream river, DOM was affected by fruit plantations and residences, contribution from upstream river could also be neglected. From the other aspects, some significant correlations were also observed, which were independent of riparian eco-system differences, for example, the SUVA280 versus S(275-295) (negative), CDOM versus FDOM (positive), and CDOM and S(275-295) (negative), indicating the correlation was an intrinsic property of DOM that could not be affected by the surrounding environment. Meanwhile, the main chromophoric component of CDOM in Changshou Lake was high molecular weight (HMW) components within highly aromatic structures. At least, 51% of CDOM dynamic could be explained by changes of FDOM, especially in backwater zone the co-variance was more obvious. Furthermore, when the traditional fluorescence index (FI) could not comprehensively explain the differences of DOM sources due to very similar (statistically insignificant) values, integration of UV-Vis and fluorescence spectral characteristics and detailed discussion of riparian eco-system differences, might be an important way to help further resolution of DOM composition and sources in aquatic environments, such as lake, river and watershed.

20.
Huan Jing Ke Xue ; 37(6): 2073-2081, 2016 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964872

RESUMO

Dissolved organic matter (DOM) is an important component in lake eco-systems. It plays a crucial role in the environmental fate of pollutants such as mercury(Hg), because of its specific characteristics and functional structures. In this study, a typical reservoir lake from inland of Three Gorges Reservoir areas, Changshou Lake was selected to track the changes of DOM geochemical properties for one year by using UV-Vis absorption spectroscopy technique. Meanwhile, based on observed Hg data in Changshou Lake, it further validated the key environmental implications of DOM for Hg distributions in lake. The results showed that as compared to January, other months including April, June and September had significantly higher CDOM, but also higher DOC with a slightly decreasing significance. Dynamics of chromphoric component is an important reason to explain the seasonal changes of DOM concentration in Changshou Lake. Chromphores of DOM were mainly derived from high molecular weight (MW) materials with high aromaticity. Also, three wavelengths fitting model of CDOM could be used for inversion of DOC concentration in annual monitoring. Meanwhile, seasonal differences of SUVA254 and S275-295 were significant. Lowest aromaticity and MW size were observed in January following an obvious increase from April. In contrast to other types of lakes, DOM aromaticity and MW size in Changshou Lake were lower than forest lakes, but higher than plateau lakes. Eco-system and land use types surrounding lakes could have a heavily impact on the heterogeneous properties of DOM. Importantly, no clear differences between concentrations of Hg species and SUVA254 and DOC respectively were observed, however chromphoric component and MW size controlled the dissolved Hg and reactive Hg in lake. Additionally, enrichment and migration of organic matter resulted from primary productivity in lake may be a substantial reason to explain the methylmercury changes.


Assuntos
Monitoramento Ambiental , Mercúrio/análise , Compostos Orgânicos/análise , Poluentes Químicos da Água/análise , China , Lagos/química , Compostos de Metilmercúrio , Análise Espectral
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