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1.
Article in Chinese | WPRIM | ID: wpr-880068

ABSTRACT

There were three new blood group systems including the KANNO blood group system, the Sid blood group system and the CTL2 blood group system (provisional status), have been registered by the International Society of Blood Transfusion (ISBT) registered Science August 2019. The main reason for this update is that the significant SNPs of the KANNO blood group system (rs1800014) and the Sid blood group system (rs7224888) have been found through genome-wide association studies and whole exome sequencing. The new genetic evidences are consistent with the current immunological findings. In addition, although CTL2 antigen has been found on erythrocyte ghost (erythrocyte membrane) since 2017, CTL2 blood group system is still in provisional status due to lack of serological and genetic evidence. In this review, the experimental research advances of these three ISBT blood group systems and discuss the clinical value of the relevant researches was summarized briefly.


Subject(s)
Blood Group Antigens , Blood Transfusion , Genome-Wide Association Study , Humans
2.
Chinese Medical Journal ; (24): 2556-2563, 2021.
Article in English | WPRIM | ID: wpr-921163

ABSTRACT

BACKGROUND@#Ankylosing spondylitis (AS) is a common chronic progressive rheumatic disease. The aim of this study was to explore factors influencing abnormal bone mineral density (BMD) in young and middle-aged patients with AS.@*METHODS@#From July 2014 to August 2018, hospitalized patients with AS and health examinees in the health examination center of our clinics, ranging in age from 20 to 50 years, were monitored. The BMD of the lumbar spine and femoral neck of AS patients and those of a healthy control group were measured using dual-energy X-ray absorption. The BMDs of AS patients were compared with respect to age, course of disease, iritis, smoking habits, sex, height, weight, body mass index (BMI), medication use, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet volume, platelet count, uric acid (UA), alkaline phosphatase (AKP), and calcium ion levels. Single-nucleotide polymorphisms (SNPs) related to BMD were screened using genome-wide association analysis.@*RESULTS@#There was no statistical difference in the proportion of abnormal bone masses between the different body parts. The BMD of all bones in AS patients was lower than that in healthy controls (P < 0.05). Additionally, BMD was correlated with serum calcium and CRP in AS patients (P < 0.05), but not with age, platelet volume, platelet count, ESR, UA, AKP, height, weight, and BMI. The incidence of abnormal bone mass in AS patients was correlated with sex (P < 0.05), but not with medication use, iritis, or smoking. BMD of the lumbar spine in AS patients did not correlate linearly with the course of the disease, but BMD of the femoral neck correlated linearly with the course of the disease (P < 0.05). BMD was correlated with multiple SNPs in patients with AS. Lumbar BMD was correlated with rs7025373 and rs7848078. Femoral head BMD was correlated with 3:102157365, 3:102157417, rs1252202, rs1681355, rs3891857, rs7842614, and rs9870734, suggesting that genetic factors play a role in BMD in patients with AS.@*CONCLUSIONS@#The proportion of abnormal bone mass in AS patients was higher than that in healthy individuals of the same age. The factors related to BMD in patients with AS are gender, CRP, and blood calcium. The BMD of the femoral neck of AS patients decreases with the course of the disease, but BMD of the lumbar spine is not related to the course of the disease. BMD in AS patients is associated with multiple SNPs.


Subject(s)
Absorptiometry, Photon , Adult , Bone Density , Femur Neck , Genome-Wide Association Study , Humans , Lumbar Vertebrae , Middle Aged , Spondylitis, Ankylosing/genetics , Young Adult
3.
Frontiers of Medicine ; (4): 275-291, 2021.
Article in English | WPRIM | ID: wpr-880954

ABSTRACT

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.


Subject(s)
Adenocarcinoma of Lung/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Squamous Cell/genetics , Genetic Heterogeneity , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Lung Neoplasms/genetics , Polymorphism, Single Nucleotide
4.
Article in Chinese | WPRIM | ID: wpr-878704

ABSTRACT

Objective To analyze the research status,hotspots,and frontiers of atherosclerosis genomics from 2010 to 2019.Methods CiteSpace software was used to conduct data statistics and visual analysis on countries,institutions,authors,journals,co-cited papers,and keywords of the related papers published in the Web of Science from 2010 to 2019.Results A total of 1021 papers in English were included,and the annual number of publications generally showed an upward trend.The knowledge base in the research of atherosclerosis mostly focused on the genetic risk sites and biomarkers for coronary artery diseases such as coronary heart disease,myocardial infarction,and dyslipidemia.The related journals mainly involved the fields of molecular biology,biology,genetics,immunology,medicine,pharmacy,and clinical medicine.The latest research in atherosclerosis concentrated on genome-wide association study,DNA methylation,microRNA,messenger RNA and so on.The research frontiers involved long noncoding RNA,DNA methylation,and immune metabolism.Conclusion The studies in atherosclerotic genomics have gradually increased.


Subject(s)
Atherosclerosis/genetics , Bibliometrics , Biomarkers , Genome-Wide Association Study , Genomics , Humans
5.
Chinese Medical Journal ; (24): 1138-1145, 2021.
Article in English | WPRIM | ID: wpr-878167

ABSTRACT

BACKGROUND@#Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women.@*METHODS@#We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.@*RESULTS@#We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (Pmeta = 2.34 × 10-8), and a previously reported SNP, rs9397435 (Pmeta = 4.32 × 10-38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.@*CONCLUSIONS@#Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.


Subject(s)
Asian Continental Ancestry Group/genetics , Breast Neoplasms/genetics , Case-Control Studies , China , Female , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide/genetics , RNA, Long Noncoding/genetics
6.
Cienc. tecnol. salud ; 8(1): 104-117, 2021. il 27 c
Article in Spanish | LILACS, LIGCSA, DIGIUSAC | ID: biblio-1352998

ABSTRACT

La autoinmunidad es la consecuencia de la pérdida de control y regulación de la respuesta inmune. Se re-porta que ocurre entre 5 y 9% de patologías a nivel mundial. A las enfermedades con esta anomalía se les denomina autoinmunes y se clasifican de acuerdo con el órgano o sistema afectado. Las reumáticas involucran al tejido conectivo y las articulaciones. Los factores asociados a su aparición incluyen: edad, género, medioam-biente y genéticos. La susceptibilidad genética indica la presencia de uno o varios genes asociados al desarrollo de determinada enfermedad, cuya expresión podría ser el producto de la migración, selección, recombinación y adaptación de genes entre las poblaciones, lo que explica la variación fenotípica y la expresión clínica resultan-te. Los estudios de asociación del genoma completo (GWAS por sus siglas en inglés) han permitido identificar múltiples genes involucrados con enfermedades reumáticas, destacan el lupus eritematoso sistémico y artritis reumatoide, asociadas con más de 60 alelos, y otras como la espondilitis anquilosante, en donde la asociación ha sido primordialmente con un gen y sus polimorfismos. Esta revisión tiene como objetivo informar el estado de la susceptibilidad determinada genéticamente para estas enfermedades y el impacto que tiene sobre la expresión clínica. Se realizó una búsqueda en PubMed y la base de datos de la biblioteca Cochrane, se incluyeron artículos relacionados con las palabras clave propuestas desde el 2000. La revisión identifica genes y la asociación con estas enfermedades, expone la diversidad existente y justifica continuar la búsqueda de genes en todas las poblaciones.


Autoimmunity is the consequence of the loss of control and regulation of the immune response. It is reported that between 5 and 9% of pathologies occur worldwide. Diseases with this abnormality are called autoimmune and are classified according to the organ or system affected. Rheumatic diseases involve connective tissue and joints. Factors associated with its appearance include age, gender, environment, and genetics. Genetic suscepti-bility indicates the presence of one or more genes associated with the development of a certain disease, whose expression could be the product of migration, selection, recombination and adaptation of genes between popu-lations, which explains the phenotypic variation and the resulting clinical expression. Genome wide association studies (GWAS) have allowed the identification of multiple genes involved with rheumatic diseases, including systemic lupus erythematosus and rheumatoid arthritis, associated with more than 60 alleles, and others such as ankylosing spondylitis, where the association has been primarily with a gene and its polymorphisms. This review aims to report the status of genetically determined susceptibility to these diseases and the impact it has on clinical expression. A search was carried out in PubMed and the Cochrane library database, articles related to the proposed keywords from the year 2000 were included. The review identifies genes and the association with these diseases, exposes the existing diversity and justifies continuing the search for genes in all populations.


Subject(s)
Humans , Arthritis, Rheumatoid/congenital , Arthritis, Rheumatoid/immunology , Genetic Research , Autoimmunity/immunology , Genetic Predisposition to Disease , Genome-Wide Association Study , Genes , Lupus Erythematosus, Systemic/congenital
7.
Article in English | WPRIM | ID: wpr-786073

ABSTRACT

OBJECTIVE: Total ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. However, recent studies have demonstrated that plasma concentrations of specific very-long-chain fatty ceramides (C24:0 and C22:0) are associated with a reduced incidence of coronary heart disease and all-cause mortality. We hypothesized that specific genetic loci are associated with plasma C22:0 and C24:0 concentrations.METHODS: Heritability and genome-wide association studies of plasma C24:0 and C22:0 ceramide concentrations were performed among 2,217 participants in the Framingham Heart Study Offspring Cohort, adjusting for cardiovascular risk factor covariates and cardiovascular drug treatment.RESULTS: The multivariable-adjusted heritability for C22:0 and C24:0 ceramides was 0.42 (standard error [SE], 0.07; p=1.8E-9) and 0.25 (SE, 0.08; p=0.00025), respectively. Nineteen single nucleotide polymorphisms (SNPs), all on chromosome 20, significantly associated with C22:0 concentrations; the closest gene to these variants was SPTLC3. The lead SNP (rs4814175) significantly associated with 3% lower plasma C22:0 concentrations (p=2.83E-11). Nine SNPs, all on chromosome 20 and close to SPTLC3, were significantly associated with C24:0 ceramide concentrations. All 9 were also significantly related to plasma C22:0 levels. The lead SNP (rs168622) was significantly associated with 10% lower plasma C24:0 ceramide concentrations (p=9.94E-09).CONCLUSION: SNPs near the SPTLC3 gene, which encodes serine palmitoyltransferase long chain base subunit 3 (SPTLC3; part of the enzyme that catalyzes the rate-limiting step of de novo sphingolipid synthesis) were associated with plasma C22:0 and C24:0 ceramide concentrations. These results are biologically plausible and suggest that SPTLC3 may be a potential therapeutic target for C24:0 and C22:0 ceramide modulation.


Subject(s)
Cardiovascular Diseases , Ceramides , Chromosomes, Human, Pair 20 , Cohort Studies , Coronary Disease , Genetic Loci , Genome-Wide Association Study , Genomics , Heart , Incidence , Insulin Resistance , Mortality , Plasma , Polymorphism, Single Nucleotide , Risk Factors , Serine C-Palmitoyltransferase
8.
Article in English | WPRIM | ID: wpr-811201

ABSTRACT

Matrix metallopeptidase 3 or MMP3, is a zinc-dependent proteolytic enzyme that is involved in various physiological processes via modification of the extracellular matrix. In particular, its over-expression has been associated with cancer metastasis and tumor growth in various cancers including breast cancer. MMP3 gene expression is regulated by several factors such as DNA polymorphisms which also serve as risk factors for breast cancer. As such, DNA polymorphisms of MMP3 have the potential to be utilized as genetic biomarkers for prediction and prognosis of metastatic breast cancer. Presently, genome-wide association studies of MMP3 gene polymorphisms which are associated with breast cancer risk and patient survival in a variety of populations are reviewed. In order to understand the potential role of MMP3 polymorphisms as genetic markers for breast cancer metastasis, the domain structure of MMP3, the regulation of its expression and its role in breast cancer metastasis are also briefly discussed in this review. The emergence of MMP3 gene polymorphisms as prognostic biomarker candidates for breast cancer metastasis may contribute towards improving targeted therapies and categorization of breast cancer cases in order to provide a better and more accurate prognosis.


Subject(s)
Biomarkers , Breast Neoplasms , Breast , DNA , Extracellular Matrix , Gene Expression , Genetic Markers , Genome-Wide Association Study , Humans , Matrix Metalloproteinase 3 , Neoplasm Metastasis , Physiological Phenomena , Prognosis , Risk Factors
9.
Chinese Medical Journal ; (24): 675-681, 2020.
Article in English | WPRIM | ID: wpr-878091

ABSTRACT

BACKGROUND@#Several recent genome-wide association studies suggested insomnia and anemia may share some common genetic components. We thus examined whether adults with anemia had higher odds of having insomnia relative to those without anemia in a cross-sectional study and a meta-analysis.@*METHODS@#Included in this cross-sectional study were 12,614 Chinese adults who participated in an ongoing cohort, the Kailuan Study. Anemia was defined as hemoglobin levels below 12.0 g/dL in women and 13.0 g/dL in men. Insomnia was assessed using the Chinese version of the Athens Insomnia Scale (AIS). A total AIS score ≥6 was considered insomnia. The association between anemia and insomnia was assessed using a logistic regression model, adjusting for potential confounders such as age, sex, chronic disease status, and plasma C-reactive protein concentrations. A meta-analysis was conducted using the fixed effects model to pool results from our study and three previously published cross-sectional studies on this topic in adult populations.@*RESULTS@#Individuals with anemia had greater odds of having insomnia (adjusted odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.03-1.70) compared with individuals without anemia. A significant association persisted after we excluded individuals with chronic inflammation, as suggested by C-reactive protein levels >1 mg/L (adjusted OR: 1.68; 95% CI: 1.22-2.32). The meta-analysis results, including 22,134 participants, also identified a positive association between anemia and insomnia (pooled OR: 1.39; 95% CI: 1.22-1.57).@*CONCLUSIONS@#The presence of anemia was significantly associated with a higher likelihood of having insomnia in adults. Due to the nature of the cross-sectional study design, results should be interpreted with caution.


Subject(s)
Adult , Anemia/epidemiology , Cohort Studies , Cross-Sectional Studies , Female , Genome-Wide Association Study , Humans , Male , Sleep Initiation and Maintenance Disorders/epidemiology
10.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(6): 485-493, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055347

ABSTRACT

Objective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.


Subject(s)
Humans , Male , Adult , Young Adult , Crack Cocaine , DNA Methylation , Cocaine-Related Disorders/genetics , Cocaine-Related Disorders/blood , Genome-Wide Association Study/methods , Case-Control Studies , Linear Models , Histone-Lysine N-Methyltransferase/genetics , Statistics, Nonparametric , Mitogen-Activated Protein Kinase 1/genetics , MAP Kinase Kinase 1/genetics , Mitogen-Activated Protein Kinase 3/genetics , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing , Histocompatibility Antigens/genetics , Histone Deacetylases/genetics
11.
Article in Chinese | WPRIM | ID: wpr-781657

ABSTRACT

To analyze the research hotspots and trends of biomarkers for diseases based on genomics and thus provide basis for the future studies in this field. Based on the Web of Science,we analyzed the genomics-based biomarkers for diseases in literature published between 2006 and 2018 in terms of country and institutions,knowledge base,research hotspots,and trends by using bibliometric methods and CiteSpace software. A total of 998 articles were retrieved.The total number of articles has shown an upward trend and reached a peak of 112 in 2017 and 2018.Most articles(=477)were from the United States,follwed by China(=93).,,,,and are core journals in this field.Keywords co-occurrence analysis identified four research hotspots:disease research,research method and technology,research level,and application purpose. Research in functional genomics,cancer immunotherapy,genome-wide association and multi-omics techniques,personalized medicine,and precision medicine are research hotspots and frontiers in this field.


Subject(s)
Bibliometrics , Biomarkers , China , Genome-Wide Association Study , Genomics , United States
12.
Article in English | WPRIM | ID: wpr-765672

ABSTRACT

Dysregulated lipid metabolism, characterized by higher levels of circulating triglycerides, higher levels of small, low density lipoprotein, and accumulation of intracellular lipids, is linked to insulin resistance and related complications such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Considering that various metabolic, genetic, and environmental factors are involved in the development of T2DM and CVD, the causalities of these diseases are often confounded. In recent years, Mendelian randomization (MR) studies coupling genetic data in population studies have revealed new insights into the risk factors influencing the development of CVD and T2DM. This review briefly conceptualizes MR and summarizes the genetic traits related to lipid metabolism by evaluating their effects on the indicators of insulin resistance based on the results of recent MR studies. The data from the MR study cases referred to in this review indicate that the causal associations between lipid status and insulin resistance in MR studies are not conclusive. Furthermore, available data on Asian ethnicities, including Korean, are very limited. More genome-wide association studies and MR studies on Asian populations should be conducted to identify Asian- or Korean-specific lipid traits in the development of insulin resistance and T2DM. The present review discusses certain studies that investigated genetic variants related to nutrient intake that can modify lipid metabolism outcomes. Up-to-date inferences on the causal association between lipids and insulin resistance using MR should be interpreted with caution because of several limitations, including pleiotropic effects and lack of information on genotype and ethnicity.


Subject(s)
Asian Continental Ancestry Group , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Genome-Wide Association Study , Genotype , Humans , Insulin Resistance , Insulin , Lipid Metabolism , Lipoproteins , Mendelian Randomization Analysis , Random Allocation , Risk Factors , Triglycerides
13.
Article in English | WPRIM | ID: wpr-763818

ABSTRACT

The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.


Subject(s)
Case-Control Studies , Dataset , Genome-Wide Association Study , Humans , Leukocytes
14.
Article in English | WPRIM | ID: wpr-763816

ABSTRACT

We sought the novel concept, transcript capacity (TC) and analyzed TC. Our approach to estimate TC was through an in silico method. TC refers to the capacity that a transcript exerts in a cell as enzyme or protein function after translation. We used the genome-wide association study (GWAS) beta effect and transcription level in RNA-sequencing to estimate TC. The trait was body fat percent and the transcript reads were obtained from the human protein atlas. The assumption was that the GWAS beta effect is the gene’s effect and TC was related to the corresponding gene effect and transcript reads. Further, we surveyed gene ontology (GO) in the highest TC and the lowest TC genes. The most frequent GOs with the highest TC were neuronal-related and cell projection organization related. The most frequent GOs with the lowest TC were wound-healing related and embryo development related. We expect that our analysis contributes to estimating TC in the diverse species and playing a benevolent role to the new bioinformatic analysis.


Subject(s)
Adipose Tissue , Computational Biology , Computer Simulation , Embryonic Development , Female , Gene Ontology , Genome-Wide Association Study , Humans , Methods , Pregnancy
15.
Article in English | WPRIM | ID: wpr-772266

ABSTRACT

Streptococcus mutans is a well-known cause of dental caries, due to its acidogenicity, aciduricity, and ability to synthesize exopolysaccharides in dental plaques. Intriguingly, not all children who carry S. mutans manifest caries, even with similar characteristics in oral hygiene, diet, and other environmental factors. This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries; however, the association between host genetics, S. mutans, and dental caries remains unclear. Therefore, this study examined the influence of host gene-by-S. mutans interaction on dental caries. Genome-wide association analyses were conducted in 709 US children (<13 years old), using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS). A generalized estimating equation was used to examine the gene-by-S. mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries). Sequentially, the COHRA and GEIRS data were used to identify potential interactions and replicate the findings. Three loci at the genes interleukin 32 (IL32), galactokinase 2 (GALK2), and CUGBP, Elav-like family member 4 (CELF4) were linked to S. mutans carriage, and there was a severity of caries at a suggestive significance level among COHRA children (P < 9 × 10), and at a nominal significance level among GEIRS children (P = 0.047-0.001). The genetic risk score that combined the three loci also significantly interacted with S. mutans (P < 0.000 1). Functional analyses indicated that the identified genes are involved in the host immune response, galactose carbohydrate metabolism, and food-rewarding system, which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.


Subject(s)
Adolescent , Child , DMF Index , Dental Caries , Microbiology , Dental Caries Susceptibility , Genetics , Galactokinase , Genome-Wide Association Study , Humans , Streptococcus mutans , Genetics , Tooth, Deciduous
16.
Neuroscience Bulletin ; (6): 561-580, 2019.
Article in English | WPRIM | ID: wpr-775436

ABSTRACT

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.


Subject(s)
Antipsychotic Agents , Asian Continental Ancestry Group , Genetics , China , Genome-Wide Association Study , Genotype , Humans , Lipid Metabolism , Genetics , Neurosecretory Systems , Pharmacogenomic Testing , Polymorphism, Single Nucleotide , Receptors, Adrenergic , Genetics , Receptors, Dopamine , Genetics , Receptors, Histamine , Genetics , Receptors, Serotonin , Genetics , Weight Gain , Genetics
17.
Article in English | WPRIM | ID: wpr-758882

ABSTRACT

Genome-wide association study (GWAS) is a powerful tool for identifying the genetic causes of various diseases. This study was conducted to identify genomic variation in Maltese dog genomes associated with degenerative mitral valve disease (DMVD) development and to evaluate the association of each biological condition with DMVD in Maltese dogs. DNA was extracted from blood samples obtained from 48 Maltese dogs (32 with DMVD and 16 controls). Genome-wide single nucleotide polymorphism (SNP) genotyping was performed. The top 30 SNPs from each association of various conditions and genetic variations were mapped to their gene locations. A total of 173,662 loci were successfully genotyped, with an overall genotype completion rate of 99.41%. Quality control analysis excluded 46,610 of these SNPs. Manhattan plots were produced using allelic tests with various candidate clinical conditions. A significant peak of association was observed between mitral valve prolapse (MVP) and SNPs on chromosome 17. The present study revealed significant SNPs in several genes associated with cardiac function, including PDZ2, Armadillo repeat protein detected in velo-cardio-facial syndrome, catenin (cadherin-associated protein) alpha 3, low-density lipoprotein receptor class A domain containing protein 4, and sterile alpha motif domain containing protein 3. To our knowledge, this is the first study of a genetic predisposition to DMVD in Maltese dogs. Although only a limited number of cases were analyzed, these data could be the basis for further research on the genetic predisposition to MVP and DMVD in Maltese dogs.


Subject(s)
Animals , Armadillos , Chromosomes, Human, Pair 17 , DiGeorge Syndrome , DNA , Dogs , Genetic Predisposition to Disease , Genetic Variation , Genome , Genome-Wide Association Study , Genotype , Mitral Valve Prolapse , Mitral Valve , Polymorphism, Single Nucleotide , Quality Control , Receptors, Lipoprotein
18.
Article in English | WPRIM | ID: wpr-785794

ABSTRACT

The achievements of genome-wide association studies have suggested ways to predict diseases, such as type 2 diabetes (T2D), using single-nucleotide polymorphisms (SNPs). Most T2D risk prediction models have used SNPs in combination with demographic variables. However, it is difficult to evaluate the pure additive contribution of genetic variants to classically used demographic models. Since prediction models include some heritable traits, such as body mass index, the contribution of SNPs using unmatched case-control samples may be underestimated. In this article, we propose a method that uses propensity score matching to avoid underestimation by matching case and control samples, thereby determining the pure additive contribution of SNPs. To illustrate the proposed propensity score matching method, we used SNP data from the Korea Association Resources project and reported SNPs from the genome-wide association study catalog. We selected various SNP sets via stepwise logistic regression (SLR), least absolute shrinkage and selection operator (LASSO), and the elastic-net (EN) algorithm. Using these SNP sets, we made predictions using SLR, LASSO, and EN as logistic regression modeling techniques. The accuracy of the predictions was compared in terms of area under the receiver operating characteristic curve (AUC). The contribution of SNPs to T2D was evaluated by the difference in the AUC between models using only demographic variables and models that included the SNPs. The largest difference among our models showed that the AUC of the model using genetic variants with demographic variables could be 0.107 higher than that of the corresponding model using only demographic variables.


Subject(s)
Area Under Curve , Body Mass Index , Case-Control Studies , Genome-Wide Association Study , Korea , Logistic Models , Methods , Polymorphism, Single Nucleotide , Propensity Score , ROC Curve
19.
Article in English | WPRIM | ID: wpr-785793

ABSTRACT

Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner's curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33–0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis.


Subject(s)
Asian Continental Ancestry Group , Bias , Genetic Variation , Genome-Wide Association Study , Glycemic Index , Humans , Liver , Phenotype , Polymorphism, Single Nucleotide , Risk Assessment
20.
Journal of Stroke ; : 276-289, 2019.
Article in English | WPRIM | ID: wpr-766263

ABSTRACT

Stroke is a complex disease and one of the main causes of morbidity and mortality among the adult population. A huge variety of factors is known to influence patient outcome, including demographic variables, comorbidities or genetics. In this review, we expound what is known about the influence of clinical variables and related genetic risk factors on ischemic stroke outcome, focusing on acute and subacute outcome (within 24 to 48 hours after stroke and until day 10, respectively), as they are the first indicators of stroke damage. We searched the PubMed data base for articles that investigated the interaction between clinical variables or genetic factors and acute or subacute stroke outcome. A total of 61 studies were finally included in this review. Regarding the data collected, the variables consistently associated with acute stroke outcome are: glucose levels, blood pressure, presence of atrial fibrillation, prior statin treatment, stroke severity, type of acute treatment performed, severe neurological complications, leukocyte levels, and genetic risk factors. Further research and international efforts are required in this field, which should include genome-wide association studies.


Subject(s)
Adult , Atrial Fibrillation , Blood Pressure , Comorbidity , Genetics , Genome-Wide Association Study , Glucose , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Leukocytes , Mortality , Risk Factors , Stroke
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