Application of Mendelian randomization in liver cancer / 临床肝胆病杂志

In recent years， the research method of Mendelian randomization based on genome-wide association studies has been widely used for etiological exploration in the medical field， which can effectively overcome the confounding biases and interference of reverse causalities in traditional observational researches with its unique advantages of the distributive randomness and timing priority of genetic variants. This article reviews the method of Mendelian randomization and its application in liver cancer， in order to provide new ideas for the research on causal association in liver cancer.

Bidirectional casual effects between periodontitis and Sjögren's syndrome: a Mendelian randomization study / 口腔疾病防治

Objective@#To evaluate the bidirectional association between periodontitis and Sjögren's syndrome using the Mendelian randomization (MR) method.@*Methods@#Genome-wide association study (GWAS) data of periodontitis (N = 45 563) and Sjögren's syndrome (N = 214 435) were selected to meet the requirements of the same ethnicity and different regions. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) tests were used to evaluate the causal effect. Cochran's Q statistics, MR-Egger intercept, MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.@*Results@#After screening, the GWAS data of Sjögren's syndrome were based on the Finnish region, and the periodontitis GWAS data were based on the UK region, both of which originated from European ancestry. Using IVW (OR = 1.017, 95% CI = 0.956-1.082), MR-Egger (OR = 0.985, 95% CI= 0.956-1.082), and WM (OR =1.021, 95% CI = 0.948-1.099), no causal effect of Sjögren's syndrome on periodontitis was found using any of the three methods. Conversely, no causal effect of periodontitis on Sjögren's syndrome was found (IVW, OR = 1.024, 95% CI = 0.852-1.230; MR-Egger, OR = 0.978, 95% CI = 0.789-1.212; WM, OR = 1.024, 95% CI = 0.846-1.260). The sensitivity analyses indicated that the results were stable and reliable. Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables, which included single nucleotide polymorphisms (SNPs). The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs. No individual SNP was found that significantly affected the results using the leave-one-out method.@*Conclusion@#This study does not support a bidirectional causal effect between periodontitis and Sjögren's syndrome.

Identification of banana ADA1 gene family members and their expression profiles under biotic and abiotic stresses / 生物工程学报

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.

Genome-wide association analysis of agronomic traits related to eggplant fruits: a review / 生物工程学报

Eggplant is an important horticultural crop and one of the most widely grown vegetables in the Solanaceae family. Eggplant fruit-related agronomic traits are complex quantitative traits with low efficiency and long cycle time for traditional breeding selection. With the rapid development of high-throughput sequencing technology and bioinformatics tools, genome-wide association study (GWAS) has shown great application potential in analyzing the genetic rules of complex agronomic traits related to eggplant fruits. This paper first reviews the progress of genome-wide association analysis in eggplant fruit shape, fruit color and other fruit-related agronomic traits. Subsequently, aiming at the problem of missing heritability, which is common in the genetic studies of eggplant quantitative traits, this paper puts forward the development strategies of eggplant GWAS in the future based on the hot spots of application of four GWAS strategies in the research of agronomics traits related to eggplant fruits. Lastly, the application of GWAS strategy in the field of eggplant molecular breeding is expected to provide a theoretical basis and reference for the future use of GWAS to analyze the genetic basis of various eggplant fruit-related traits and to select fruit materials that meet consumer needs.

Genome-wide DNA methylation and transcriptome expression profiles of peripheral blood mononuclear cells in patients with systemic sclerosis with interstitial lung disease / 中南大学学报(医学版)

OBJECTIVES@#This study aims to investigate the genome-wide DNA methylation and transcriptome expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with systemic sclerosis (SSc) with interstitial lung disease (ILD), and to analyze the effects of DNA methylation on Wnt/β-catenin and chemokine signaling pathways.@*METHODS@#PBMCs were collected from 19 patients with SSc (SSc group) and 18 healthy persons (control group). Among SSc patients, there were 10 patients with ILD (SSc with ILD subgroup) and 9 patients without ILD (SSc without ILD subgroup). The genome-wide DNA methylation and gene expression level were analyzed by using Illumina 450K methylation chip and Illumina HT-12 v4.0 gene expression profiling chip. The effect of DNA methylation on Wnt/β-catenin and chemokine signal pathways was investigated.@*RESULTS@#Genome-wide DNA methylation analysis identified 71 hypermethylated CpG sites and 98 hypomethylated CpG sites in the SSc with ILD subgroup compared with the SSc without ILD subgroup. Transcriptome analysis distinguished 164 upregulated genes and 191 downregulated genes in the SSc with ILD subgroup as compared with the SSc without ILD subgroup. In PBMCs of the SSc group, 35 genes in Wnt/β-catenin signaling pathway were hypomethylated, while frizzled-1 (FZD1), mitogen-activated protein kinase 9 (MAPK9), mothers against DPP homolog 2 (SMAD2), transcription factor 7-like 2 (TCF7L2), and wingless-type MMTV integration site family, member 5B (WNT5B) mRNA expressions were upregulated as compared with the control group (all P<0.05). Compared with the SSc without ILD subgroup, the mRNA expressions of dickkopf homolog 2 (DKK2), FZD1, MAPK9 were upregulated in the SSc with ILD subgroup, but the differences were not statistically significant (all P>0.05). In PBMCs of the SSc group, 38 genes in chemokine signaling pathway were hypomethylated, while β-arrestin 1 (ARRB1), C-X-C motif chemokine ligand 10 (CXCL10), C-X-C motif chemokine ligand 16 (CXCL16), FGR, and neutrophil cytosolic factor 1C (NCF1C) mRNA expressions were upregulated as compared with the control group (all P<0.05). Compared with the SSc without ILD subgroup, the mRNA expressions of ARRB1, CXCL10, CXCL16 were upregulated in the SSc with ILD subgroup, but the differences were not statistically significant (all P>0.05).@*CONCLUSIONS@#There are differences in DNA methylation and transcriptome profiles between SSc with ILD and SSc without ILD. The expression levels of multiple genes in Wnt/β- catenin and chemokine signaling pathways are upregulated, which might be associatea with the pathogenesis of SSc.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data / 中南大学学报(医学版)

OBJECTIVES@#Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms.@*METHODS@#Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants.@*RESULTS@#MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH.@*CONCLUSIONS@#There is a causal association and pleiotropic variants between GM and ICH.

Screening of pathogenic molecular markers of Staphylococcus aureus in children based on whole genome sequencing technology / 中国当代儿科杂志

OBJECTIVES@#To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus.@*METHODS@#A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers.@*RESULTS@#A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68).@*CONCLUSIONS@#The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

Molecular characterization of mutations associated with resistance among 72 multidrug-resistant strains of Mycobacterium tuberculosis by whole genome sequencing / 中国热带医学

@#Abstract: Objective　To understand the characteristics of mutations associated with resistance among 72 multidrug-resistant tuberculosis (MDR-TB) strains using whole genome sequencing (WGS) and to evaluate the performance of WGS for predicting MDR-TB drug resistance. Methods　The clinical strains isolated from patients who visited the outpatient department of Tianjin Center for Tuberculosis Control from January to September in 2020 were collected. Identification tests using p-nitrobenzoic acid (PNB) medium were performed. Drug susceptibility tests (proportion method) on L-J medium were performed. After excluding duplicate strains, 72 MDR-TB strains were selected for WGS. Data were analyzed by using online databases and the phenotypic drug susceptibility test results were compared with resistance profiles predicted by WGS. Results　All of 72 MDR-TB strains belonged to linage 2, and there was no significant difference in rate of pre-extensive drug-resistant tuberculosis (pre-XDR-TB) between modern type and ancestral type (χ2=0.287, P=0.592). A total of 81 mutation types were found from resistance-related genes for 12 anti-tuberculosis drugs, and the common mutation types in different drug-resistant strains were: streptomycin (SM): rpsL Lys43Arg; isoniazid (INH): katG Ser315Thr; rifampicin (RIF): rpoB Ser450Leu; ethambutol (EMB): embB Met306Val; ofloxacin (OFX), levofloxacin (LFX), moxifloxacin (MFX): gyrA Asp94Gly; kanamycin (KAM), capreomycin (CAP), amikacin (AMK): rrs 1401a>g; para-aminosalicylic acid (PAS): folC Ile43Thr. Nine mutation types were found in 9 prothionamide (PTO)-resistant strains, one type for each strain. The sensitivity and specificity of WGS for predicting resistance to different drugs were SM: 98.15% and 88.89%, INH: 90.28% and -, RIF: 98.62% and -, EMB: 79.49% and75.76%, OFX: 97.30% and 85.71%, KAM: 85.71% and 98.46%, PAS: 27.27% and 95.08%, PTO: 81.82% and 60.66%, CAP: 60.00% and 98.51%, LFX: 97.22% and 83.33%, MFX: 97.30% and 85.71%, AMK:100.00% and 100.00%, respectively. Conclusion　WGS is a rapid and promising method which has high consistency with the phenotypic drug sensitivity test. Therefore, it has good application prospects in predicting drug resistance in MDR-TB.

How data science and AI-based technologies impact genomics

Advancements in high-throughput sequencing have yielded vast amounts of genomic data, which are studied using genome-wide association study (GWAS)/phenome-wide association study (PheWAS) methods to identify associations between the genotype and phenotype. The associated findings have contributed to pharmacogenomics and improved clinical decision support at the point of care in many healthcare systems. However, the accumulation of genomic data from sequencing and clinical data from electronic health records (EHRs) poses significant challenges for data scientists. Following the rise of artificial intelligence (AI) technology such as machine learning and deep learning, an increasing number of GWAS/PheWAS studies have successfully leveraged this technology to overcome the aforementioned challenges. In this review, we focus on the application of data science and AI technology in three areas, including risk prediction and identification of causal single-nucleotide polymorphisms, EHR-based phenotyping and CRISPR guide RNA design. Additionally, we highlight a few emerging AI technologies, such as transfer learning and multi-view learning, which will or have started to benefit genomic studies.

Association of ticagrelor with risk of infection：a two-sample Mendelian randomization study based on the GWAS database / 中国药房

OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae，acute upper respiratory infection and sepsis were furtheranalyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415） pleiotropy tests. RESULTS The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris （P＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），P＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98）， P＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （P＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （P＞0.05）. CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.

Association between exonic polymorphisms of human leukocyte antigen-G gene and non-segmental vitiligo in the Korean population

Background: Vitiligo is a pigmentary skin disorder characterised by a chronic and progressive loss of melanocytes. Although several theories have been suggested to the pathogenesis of vitiligo, an autoimmune process leading to melanocyte destruction appears most likely. Human leukocyte antigen-G is a non-classic, major histocompatibility complex Class I molecule that plays an important role in the suppression of the immune response. Several recent studies have provided evidences that polymorphisms in the human leukocyte antigen-G gene might be related with autoimmune diseases. Objectives: The aim of this study was to decide whether exonic single nucleotide polymorphisms in human leukocyte antigen-G contribute to the risk of developing non-segmental vitiligo in the Korean population. Methods: To evaluate the associations between exonic single nucleotide polymorphisms (rs1630223 [Ala5Ala] and rs12722477 [Leu134Ile]) of human leukocyte antigen-G and vitiligo, 244 patients with vitiligo and 398 healthy controls were recruited. Genotyping was performed using Fluidigm 192.24 Dynamic Array with EP1 (Fluidigm Corp., CA). The SNP type assay (Fluidigm Corp., CA), which employs allele-specifically designed fluorescences (FAM or VIC) primers and a common reverse primer was applied and the data were analysed using the EP1 single nucleotide polymorphisms genotyping analysis software to obtain genotype calls. Results: Two exonic single nucleotide polymorphisms (rs1630223 and rs12722477) exhibited significant associations with susceptibility and remained a statistically significant association following Bonferroni correction. These two single nucleotide polymorphisms were located within a block of linkage disequilibrium. Haplotypes G-C and A-A comprising rs1630223 and rs12722477 demonstrated a significant association with non-segmental vitiligo. Limitations: The protein expression level of patients with vitiligo and controls was not studied and a replication study of the genetic association in an independent group was not managed. Conclusion: Our results suggest that exonic human leukocyte antigen-G polymorphisms (rs1630223 and rs12722477) are associated with the development of non-segmental vitiligo.

Genome-wide identification and transcriptional profiling analysis of PIN/PILS auxin transporter gene families in Panax ginseng / 中草药·英文版

Objective: Plant hormones act as chemical messengers in the regulation of plant development and metabolism. The production of ginsenosides in Panax hybrid is promoted by auxins that are transported and accumulated by PIN-FORMED (PIN) and PIN-LIKES (PILS) auxin transporters. However, genome-wide studies of PIN/PILS of ginseng are still scarce. In current study, identification and transcriptional profiling of PIN/PILS gene families, as well as their potential relationship with ginsenoside biosynthesis in Panax ginseng were investigated. Methods: PIN/PILS genes in P. ginseng was identified via in silico genome-wide analysis, followed by phylogenetic relationships, gene structure, and protein profiles investigation. Moreover, previously reported RNA-sequence data from various tissues and roots after infection were utilized for PIN/PILS genes expression pattern analysis. The Pearson's correlation analysis of specific PIN/PILS genes expression level and main ginsenoside contents were taken to reveal the potential relationship between auxin transports and ginsenoside biosynthesis in P. ginseng. Results: A genome-wide search of P. ginseng genome for homologous auxin transporter genes identified a total of 17 PIN and 11 PILS genes. Sequence alignment, putative motif organization, and sub-cellular localization indicated redundant and complementary biological functions of these PIN/PILS genes. Most PIN/PILS genes were differentially expressed in a tissue-specific manner, and showed significant correlations with ginsenoside content correspondingly. Eight auxin transporter genes, including both PIN and PILS subfamily members, were positively correlated with ginsenoside content (cor > 0.60; P-value <0.05). The expression levels of eleven auxin transporter genes were increased dramatically in the early stage (0–0.5 DPI) after Cylindrocarpon destructans infection, accompanied with various overall expression patterns, implying the dynamic auxin transport in response to biotic stress. Conclusion: Based on the results, we speculate that the accumulation or depletion in temporal or spatial manner of auxin by PIN/PILS transporters involved in the regulation of HMGR activity and subsequent ginsenoside biosynthesis.

Genetic studies of primary biliary cholangitis in the post-GWAS era / 临床肝胆病杂志

With the constant increase in the awareness of primary biliary cholangitis (PBC) and the continuous improvement in related diagnostic methods in the past two decades, the incidence and prevalence rates of PBC tend to increase and PBC is now the most common autoimmune liver disease worldwide. A series of family-based studies in the early stage have shown that PBC has strong genetic tendency, and subsequent genomic analyses have been performed for PBC in different populations and have obtained a large amount of genetic data. Future genetic studies of PBC will focus on translating these results into clinical practice.

Progress in genetic epidemiology of gestational diabetes mellitus / 中华围产医学杂志

Gestational diabetes mellitus poses a substantial threat to the short- and long-term health of women and their offspring. Previous studies have identified a number of genetic risk factors for gestational diabetes through candidate gene strategy and whole genome studies. Many of these identified genetic variations have also been proved to be associated with type 2 diabetes, abnormal glycometabolism as well as insulin secretion and resistance. This article reviews the recent progress in the genetic epidemiology of gestational diabetes mellitus.

Modelos multivariados en la búsqueda de regiones genómicas para resistencia a mal de río cuarto y bacteriosis en maíz / Multi-trait models for genomic regions associated with mal de río cuarto and bacterial disease in maize

RESUMEN La producción de maíz (Zea Mays L.) ha sido ampliamente beneficiada con la mejora de líneas endocriadas respecto a la resistencia a enfermedades causadas por virus y hongos. Sin embargo, es notable la ausencia de genotipos resistentes a bacteriosis. El objetivo del presente estudio fue identificar regiones genómicas para la mejora de resistencia a Mal de Río Cuarto (MRC) y a bacteriosis (BD) en un germoplasma diverso de maíz. Se evaluó, para ambas enfermedades, una población diversa de líneas de maíz en el ciclo de cultivo 2019-2020 en la región argentina donde la virosis MRC es endémica. Se estimó incidencia y severidad de MRC y BD en cada línea y se realizó un estudio de mapeo por asociación (GWAS) con 78.376 marcadores SNPs. Un modelo multicarácter se utilizó para evaluar simultáneamente la resistencia a MRC y BD en las líneas evaluadas. El germoplasma evidenció alta variabilidad genética tanto para la mejora de la resistencia a MRC como a BD, pero no se observó correlación genética significativa entre la respuesta a ambas enfermedades. Se identificaron regiones genómicas promisorias para resistencia a MRC y a BD, que serán confirmadas en evaluaciones en nuevos ambientes.

ABSTRACT Maize (Zea Mays L.) production has been greatly benefited from the improvement of inbred lines in regard to the resistance to diseases. However, the absence of resistant genotypes to bacteriosis is remarkable. The aim of the study was to identify genomic regions for resistance to Mal de Río Cuarto (MRC) and to bacterial disease (BD) in a diverse maize germplasm evaluated in the Argentinian region where MRC virus is endemic. A maize diverse population was assessed for both diseases during the 2019-2020 crop season. Incidence and severity of MRC and BD were estimated for each line and a genome wide association study (GWAS) was conducted with 78,376 SNP markers. A multi-trait mixed linear model was used for simultaneous evaluation of resistance to MRC and BD in the scored lines. The germplasm showed high genetic variability for both MRC and BD resistance. No significant genetic correlation was observed between the response to both diseases. Promising genomic regions for resistance to MRC and BD were identified and will be confirmed in further trials.

A longitudinal study of transcriptional profiling of carbon-ions exposure on the lung / 中华放射肿瘤学杂志

Objective:To investigate the expression changes at the transcriptional level in normal lung tissues of mice after exposure to heavy ion radiation for different durations at different doses, aiming to provide evidence for exploring sensitive genes of heavy ion radiation, heavy ion radiation effect and the damage mechanism.Methods:Experiments on the temporal kinetics: the whole thorax of mice was irradiated with 14.5Gy carbon-ions and the total RNA of lung tissue was extracted at 3days, 7days, 3 weeks and 24 weeks. In dose-dependent experiment, the total RNA of lung tissue was extracted at 1 week after irradiated with a growing thoracic dose of 0, 7.5, 10.5, 12.5, 14.5, 17.5 and 20Gy. Protein-to-protein interaction (PPI) analysis and gene-ontology biological process enrichment analysis were performed on significant differentially expressed genes (DEGs).Results:A clearly differential expression patterns were observed at 3-day (acute stage), 1-week (subacute stage), 3-week (inflammatory stage) and 24-week (fibrosis stage) following 14.5Gy carbon-ions irradiation. Among those, the 3-day time point was found to be the mostly different from the other time points, whereas the 7-day time point had the highest uniformity with the other time points. Cellular apoptosis was the main type of cell death in normal lung tissues following carbon-ions exposure. The interactive genes of Phlda3, GDF15, Mgmt and Bax were identified as the radiosensitive genes, and Phlda3 was the center ( R=0.76, P<0.001). Conclusion:The findings in this study provide transcriptional insights into the biological mechanism underlying normal lung tissue toxicity induced by carbon-ions.

Advances in the study of POAG-related genes and central nervous system diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#In recent years, considerable progress has been made in the study of glaucoma, especially primary open angle glaucoma(POAG). A series of POAG genes has been identified through genetic linkage analysis and genome-wide association studies(GWAS), which significantly advanced the study of glaucoma genetics. The latest perspective suggests that glaucoma is a disease of the central nervous system(CNS). A large number of basic clinical studies have demonstrated the close association between CNS disease and glaucoma. Among these studies, discoveries related to genetics are of prominence.

Polymorphism of urate transporter in gout and its correlation with gout treatment / 中国组织工程研究

BACKGROUND: Urate transporters such as GLUT9, URAT1, NPT1 and ABCG2 are directly involved in the regulation of human serum uric acid levels. The gene polymorphism of urate transporter is closely related to the occurrence and development of gout. Therefore, the targeted therapy of urate transporter is a new way to treat gout. OBJECTIVE: To summarize the research progress of polymorphism expression of urate transporter in gout and its correlation with clinical drugs in recent years, therefore providing literature and theoretical basis for further exploration of personalized treatment of gout and hyperuricemia. METHODS: The first author searched CNKI, WanFang database and PubMed database. The key words were “Gout, Urate transporter, Hyperuricemia, Polymorphism, GWAS, Therapy” in Chinese and English, respectively. Totally 131 literatures were retrieved. According to the inclusion and exclusion criteria, 78 articles regarding the genetic polymorphism of urate transporter in gout and the correlation between the mechanism of action of gout drugs and urate transporter were screened out and summarized. RESULTS AND CONCLUSION: A large number of studies have shown that urate transporter polymorphism is closely related to uric acid homeostasis, with GLUT9, URAT1, NPT1 and ABCG2 being the most important. These proteins are differentially expressed in different populations and are closely related to the reaction mechanism of gout drugs. In the future diagnosis and treatment, the results of these studies can help assess the need for treatment in patients with hyperuricemia, and help patients with gout formulate personalized and effective treatment plans. It may be a feasible solution to treat hyperuricemia by activating BCRP to enhance the clearance of uric acid in the intestine.

Genome-wide association analysis reveals regulation of at-risk loci by DNA methylation in prostate cancer / 亚洲男科学杂志(英文版)

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations. Prostate cancer (PCa) is characterized by variable clinical manifestations and frequently unpredictable outcomes. We performed an expression quantitative trait loci (eQTL) analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information. Using multi-level information published in The Cancer Genome Atlas, we performed eQTL-based analyses on DNA methylation and gene expression. To better interpret these data, we correlated loci and clinical indexes to identify the important loci for both PCa development and progression. Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa, these genes are enriched in important cancer-related groups. In addition, single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci, including the 19q13.2-q13.43 and 16q22.2-q23.1 loci. Further, an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation. Although DNA methylation-regulated genes across PCa samples are a small proportion, the associated genes play important roles in PCa carcinogenesis.

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma / 医学前沿

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.