Gene-gene interaction (GGI) analysis is known to play an important role in explaining missing heritability. Many previous studies have already proposed software to analyze GGI, but most methods focus on a binary phenotype in a case-control design. In this study, we developed “Hierarchical structural CoMponent analysis of Gene-Gene Interactions” (HisCoM-GGI) software for GGI analysis with a continuous phenotype. The HisCoM-GGI method considers hierarchical structural relationships between genes and single nucleotide polymorphisms (SNPs), enabling both gene-level and SNP-level interaction analysis in a single model. Furthermore, this software accepts various types of genomic data and supports data management and multithreading to improve the efficiency of genome-wide association study data analysis. We expect that HisCoM-GGI software will provide advanced accessibility to researchers in genetic interaction studies and a more effective way to understand biological mechanisms of complex diseases.
Case-Control Studies ; Genome-Wide Association Study ; Methods ; Phenotype ; Polymorphism, Single Nucleotide ; Statistics as Topic

With the success of the genome-wide association studies (GWASs), many candidate loci for complex human diseases have been reported in the GWAS catalog. Recently, many disease prediction models based on penalized regression or statistical learning methods were proposed using candidate causal variants from significant single-nucleotide polymorphisms of GWASs. However, there have been only a few systematic studies comparing existing methods. In this study, we first constructed risk prediction models, such as stepwise linear regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN), using a GWAS chip and GWAS catalog. We then compared the prediction accuracy by calculating the mean square error (MSE) value on data from the Korea Association Resource (KARE) with body mass index. Our results show that SLR provides a smaller MSE value than the other methods, while the numbers of selected variables in each model were similar.
Body Mass Index* ; Decision Support Techniques ; Genome-Wide Association Study ; Humans ; Korea ; Learning ; Linear Models

The success of genome-wide association studies (GWASs) has enabled us to improve risk assessment and provide novel genetic variants for diagnosis, prevention, and treatment. However, most variants discovered by GWASs have been reported to have very small effect sizes on complex human diseases, which has been a big hurdle in building risk prediction models. Recently, many statistical approaches based on penalized regression have been developed to solve the “large p and small n” problem. In this report, we evaluated the performance of several statistical methods for predicting a binary trait: stepwise logistic regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN). We first built a prediction model by combining variable selection and prediction methods for type 2 diabetes using Affymetrix Genome-Wide Human SNP Array 5.0 from the Korean Association Resource project. We assessed the risk prediction performance using area under the receiver operating characteristic curve (AUC) for the internal and external validation datasets. In the internal validation, SLR-LASSO and SLR-EN tended to yield more accurate predictions than other combinations. During the external validation, the SLR-SLR and SLR-EN combinations achieved the highest AUC of 0.726. We propose these combinations as a potentially powerful risk prediction model for type 2 diabetes.
Area Under Curve ; Dataset ; Decision Support Techniques ; Diabetes Mellitus, Type 2 ; Diagnosis ; Genome-Wide Association Study* ; Humans ; Logistic Models ; Risk Assessment ; ROC Curve

The aim of this study was to determe the age-specific rubella seroprevalence and the related factors in Korean children. Subjects of the study were 5,393 students from 8 elementary schools in Gyeonggi Province, Korea. Questionnaire surveys with blood sampling were conducted in 1993, 1996, and 1999. ELISA tests, used to detect rubella specific IgG antibody, were Imx & (Abbott, U.S.A.) in 1993 and 1999, and Enzygnost & (Behring, Germany) in 1996. The age-adjusted rubella susceptibility rate was 22.9% (95% CI: 22.8-23.0%) and it increased with age from 14% to 28%. The susceptibility rates of vaccinees, nonvaccinees, and the unknown group were 21%, 35%, and 27%, respectively (p=0.000). The rates by parental education levels for elementary and below, middle school, high school, and college and over were 37%, 26%, 24%, and 20%, respectively. The geometric mean titers (GMTs) of nonvaccinees, the unknown group, and vaccinees were 47 IU/mL, 42 IU/mL, and 37 IU/mL, respectively (p=0.000). The susceptibility level was too high to prevent the rubella epidemic in Korea, which necessitates a programme that will enhance the coverage for 1st and 2nd MMR vaccination among school children. In particular, more attention should be paid to the vaccination of the children whose parental education level is relatively low.
Age Distribution ; Antibodies, Viral/blood ; Child ; Data Collection ; Female ; Human ; Immunoglobulin G/blood ; Korea/epidemiology ; Male ; Rubella/*epidemiology/immunology/prevention & control ; Rubella Vaccine ; Seroepidemiologic Studies

OBJECTIVES: The purpose of this study was firstly to introduce a Participatory Action-Oriented Training (PAOT) program for the prevention of work-related musculoskeletal diseases (WRMSDs) in Small and Medium sized Enterprises in the Gumi Industrial Zone, and secondly to assess its effect. METHODS: Two PAOT workshops to prevent WRMSDs were conducted with 39 volunteer participants from 10 companies selected (on a first-come, first-served basis) among 200 small- or medium-sized enterprises in Gumi. These companies had been provided with mandatory occupational health management agency services for Small and Medium sized Enterprises by an occupational medicine clinic. Each workshop consisted of 6 technical sessions and one closing ceremony. At the 1st session, the principles of each action checklist item were explained and an on-site checklist exercise was carried out. The 2nd to 5th sessions presented good example pictures on 4 subjects: material storage and handling, working environment, work organization and work-related welfare. Group discussions were carried out by the participants. In the final 6th session on the implementation of improvement, each participant was asked to present 6 action plans, 3 short-term and 3 long-term, for their own workplace improvement. RESULTS: Overall, the participants worked out 47 real action plans, 27 short-term and 20 long-term, for improvement of their own workplaces. Three to 6 months after the workshops, through in-person visits to each company, it was confirmed that more than half of these 47 plans had been completed; 25 plans (53.2%) had been completed as planned, 8 (17.0%) were in processing, and 14 (29.8%) had not yet been put into practice. CONCLUSIONS: The study findings confirmed that the PAOT program holds strong potential as an intervention method to prevent WRMSDs in Small and Medium sized Enterprises, although the final results have not been fully assessed yet.
Checklist ; Education ; Gyeongsangbuk-do ; Musculoskeletal Diseases ; Occupational Health ; Occupational Medicine ; Volunteers

This study evaluated the feasibility of using texture analysis and machine learning to distinguish radiographic lung patterns. A total of 1200 regions of interest (ROIs) including four specific lung patterns (normal, alveolar, bronchial, and unstructured interstitial) were obtained from 512 thoracic radiographs of 252 dogs and 65 cats. Forty-four texture parameters based on eight methods of texture analysis (first-order statistics, spatial gray-level-dependence matrices, gray-level-difference statistics, gray-level run length image statistics, neighborhood gray-tone difference matrices, fractal dimension texture analysis, Fourier power spectrum, and Law's texture energy measures) were used to extract textural features from the ROIs. The texture parameters of each lung pattern were compared and used for training and testing of artificial neural networks. Classification performance was evaluated by calculating accuracy and the area under the receiver operating characteristic curve (AUC). Forty texture parameters showed significant differences between the lung patterns. The accuracy of lung pattern classification was 99.1% in the training dataset and 91.9% in the testing dataset. The AUCs were above 0.98 in the training set and above 0.92 in the testing dataset. Texture analysis and machine learning algorithms may potentially facilitate the evaluation of medical images.
Animals ; Area Under Curve ; Cats ; Classification ; Dataset ; Dogs ; Fourier Analysis ; Fractals ; Lung ; Machine Learning ; Neural Networks (Computer) ; Pattern Recognition, Visual ; Radiography, Thoracic ; Residence Characteristics ; ROC Curve

Despite the rarity in incidence and prevalence, gastrointestinal stromal tumor (GIST) has emerged as a distinct pathogenetic entity. And the clinical management of GIST has been evolving very rapidly due to the recent recognition of its oncogenic signal transduction pathway and the introduction of new molecular-targeted therapy. Successful management of GIST requires a multidisciplinary approach firmly based on accurate histopathologic diagnosis. However, there was no standardized guideline for the management of Korean GIST patients. In 2007, the Korean GIST study group (KGSG) published the first guideline for optimal diagnosis and treatment of GIST in Korea. As the second version of the guideline, we herein have updated recent clinical recommendations and reflected changes in diagnosis, surgical and medical treatments for more optimal clinical practice for GIST in Korea. We hope the guideline can be of help in enhancing the quality of diagnosis by members of the Korean associate of physicians involving in GIST patients's care and subsequently in achieving optimal efficacy of treatment.
Antineoplastic Agents/therapeutic use ; Gastrointestinal Stromal Tumors/*pathology/surgery/*therapy ; Humans ; Neoadjuvant Therapy ; Piperazines/therapeutic use ; Proto-Oncogene Proteins c-kit/metabolism ; Pyrimidines/therapeutic use ; Recurrence ; Republic of Korea ; Tumor Markers, Biological/metabolism

OBJECTIVES: Previous genome-wide association studies have indicated the association between ankyrin 3 (ANK3) and the vulnerability of schizophrenia. We investigated the association between single nucleotide polymorphisms (SNPs) covering the whole ANK3 locus and schizophrenia in the Korean population. METHODS: The study subjects were 582 patients with schizophrenia and 502 healthy controls. Thirty-eight tag SNPs on ANK3 and five additional SNPs showing significant association with schizophrenia in previous studies were genotyped. RESULTS: Three (rs10994181, rs16914791, rs1938526) of 43 SNPs showed a nominally significant association (p < 0.05) with at least one genotype model. But none of these associations remained significant after adjusting for multiple testing errors with Bonferroni's correction. CONCLUSIONS: We could not identify a significant association between ANK3 and schizophrenia in the Korean population. However, three SNPs showing an association signal with nominal significance need to be investigated in future studies with higher statistical power and more specific phenotype crossing the current diagnostic categories.
Ankyrins ; Genetic Association Studies ; Genome-Wide Association Study ; Genotype ; Humans ; Phenotype ; Polymorphism, Single Nucleotide ; Schizophrenia*

Despite their rarity in incidence and prevalence, gastrointestinal stromal tumors (GISTs) have emerged as a distinct and noteworthy pathogenetic entity. The clinical management of GISTs has rapidly evolved due to the recent elucidation of their oncogenic signal transduction pathway and the introduction of molecular-targeted therapies. Successful management of GISTs requires a multidisciplinary approach firmly based on an accurate histopathologic diagnosis. In 2007, the Korean GIST study group published the first guideline for optimal diagnosis and treatment of GISTs in Korea. The second version of the guideline was published in 2010. Herein, we provide the results of relevant clinical studies for the purpose of further revision to the guideline. We expect this new guideline will enhance the accuracy of diagnosis, as performed by members of the Korean associate of physicians involved in GIST patient care, thus improving the efficacy of treatment.
Benzamides ; Gastrointestinal Stromal Tumors ; Incidence ; Indoles ; Korea ; Molecular Targeted Therapy ; Patient Care ; Piperazines ; Prevalence ; Pyrimidines ; Pyrroles ; Signal Transduction ; Imatinib Mesylate

Human bone marrow mesenchymal stem cells (MSCs) expanded in vitro exhibit not only a tendency to lose their proliferative potential, homing ability and telomere length but also genetic or epigenetic modifications, resulting in senescence. We compared differential methylation patterns of genes and miRNAs between early-passage [passage 5 (P5)] and late-passage (P15) cells and estimated the relationship between senescence and DNA methylation patterns. When we examined hypermethylated genes (methylation peak > or = 2) at P5 or P15, 2,739 genes, including those related to fructose and mannose metabolism and calcium signaling pathways, and 2,587 genes, including those related to DNA replication, cell cycle and the PPAR signaling pathway, were hypermethylated at P5 and P15, respectively. There was common hypermethylation of 1,205 genes at both P5 and P15. In addition, genes that were hypermethylated at P5 (CPEB1, GMPPA, CDKN1A, TBX2, SMAD9 and MCM2) showed lower mRNA expression than did those hypermethylated at P15, whereas genes that were hypermethylated at P15 (MAML2, FEN1 and CDK4) showed lower mRNA expression than did those that were hypermethylated at P5, demonstrating that hypermethylation at DNA promoter regions inhibited gene expression and that hypomethylation increased gene expression. In the case of hypermethylation on miRNA, 27 miRNAs were hypermethylated at P5, whereas 44 miRNAs were hypermethylated at P15. These results show that hypermethylation increases at genes related to DNA replication, cell cycle and adipogenic differentiation due to long-term culture, which may in part affect MSC senescence.
Bone Marrow Cells/*metabolism ; *DNA Methylation ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Mesenchymal Stromal Cells/*metabolism ; MicroRNAs ; Molecular Sequence Annotation ; Primary Cell Culture ; Promoter Regions, Genetic ; Reproducibility of Results ; Signal Transduction ; Telomere Shortening