Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are comorbidities that result from the sharing of common genes. The molecular background of comorbidities can provide clues for the development of treatment and management strategies. Here, the common genes involved in the development of the two diseases and in memory and cognitive function are reviewed.

Molecular Mechanisms of Endometriosis Revealed Using Omics Data.

Endometriosis is a gynecological disorder prevalent in women of reproductive age. The primary symptoms include dysmenorrhea, irregular menstruation, and infertility. However, the pathogenesis of endometriosis remains unclear.

Urine Metabolite of Mice with Orientia tsutsugamushi Infection.

Scrub typhus is an acute febrile, mite-borne disease endemic to the Asia-Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis-tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection.

Identification of a pleiotropic effect of ADIPOQ on cardiac dysfunction and Alzheimer's disease based on genetic evidence and health care records.

Observations of comorbidity in heart diseases, including cardiac dysfunction (CD) are increasing, including and cognitive impairment, such as Alzheimer's disease and dementia (AD/D). This comorbidity might be due to a pleiotropic effect of genetic variants shared between CD and AD/D. Here, we validated comorbidity of CD and AD/D based on diagnostic records from millions of patients in Korea and the University of California, San Francisco Medical Center (odds ratio 11.

Uncovering Oncogenic Mechanisms of Tumor Suppressor Genes in Breast Cancer Multi-Omics Data.

Tumor suppressor genes (TSGs) are essential genes in the development of cancer. While they have many roles in normal cells, mutation and dysregulation of the TSGs result in aberrant molecular processes in cancer cells. Therefore, understanding TSGs and their roles in the oncogenic process is crucial for prevention and treatment of cancer.

MPI-GWAS: a supercomputing-aided permutation approach for genomewide association studies.

Permutation testing is a robust and popular approach for significance testing in genomic research that has the advantage of reducing inflated type 1 error rates; however, its computational cost is notorious in genome-wide association studies (GWAS). Here, we developed a supercomputing-aided approach to accelerate the permutation testing for GWAS, based on the message-passing interface (MPI) on parallel computing architecture. Our application, called MPI-GWAS, conducts MPI-based permutation testing using a parallel computing approach with our supercomputing system, Nurion (8,305 compute nodes, and 563,740 central processing units [CPUs]).

A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences.

Genome-wide association studies have expanded our understanding of the genetic variation of hypertension. Hypertension and blood pressure are influenced by sex-specific differences; therefore, genetic variants may have sex-specific effects on phenotype. To identify the genetic factors influencing the sex-specific differences concerning hypertension, we conducted a heterogeneity analysis of a genome-wide association study (GWAS) on 13,926 samples from a Korean population.

Set-Wise Differential Interaction Between Copy Number Alterations and Gene Expressions of Lower-Grade Glioma Reveals Prognosis-Associated Pathways.

The integrative analysis of copy number alteration (CNA) and gene expression (GE) is an essential part of cancer research considering the impact of CNAs on cancer progression and prognosis. In this research, an integrative analysis was performed with generalized differentially coexpressed gene sets (gdCoxS), which is a modification of dCoxS. In gdCoxS, set-wise interaction is measured using the correlation of sample-wise distances with Renyi's relative entropy, which requires an estimation of sample density based on omics profiles.

Exome Chip Analysis of 14,026 Koreans Reveals Known and Newly Discovered Genetic Loci Associated with Type 2 Diabetes Mellitus.

Background: Most loci associated with type 2 diabetes mellitus (T2DM) discovered to date are within noncoding regions of unknown functional significance. By contrast, exonic regions have advantages for biological interpretation.

Methods: We analyzed the association of exome array data from 14,026 Koreans to identify susceptible exonic loci for T2DM.

KRGDB: the large-scale variant database of 1722 Koreans based on whole genome sequencing.

Since 2012, the Center for Genome Science of the Korea National Institute of Health (KNIH) has been sequencing complete genomes of 1722 Korean individuals. As a result, more than 32 million variant sites have been identified, and a large proportion of the variant sites have been detected for the first time. In this article, we describe the Korean Reference Genome Database (KRGDB) and its genome browser.

Quantitative Evaluation of Liver Fibrosis on T1 Relaxometry in Comparison with Fibroscan.

Purpose: This study was performed to determine whether the T1 relaxation time of gadoxetic acid-enhanced liver MR imaging is useful for detecting and staging liver fibrosis in patients with chronic liver disease.

Materials And Methods: One hundred and three patients with suspected focal liver lesion underwent MR imaging and Fibroscan. Fibroscan was chosen as the reference standard for classifying liver fibrosis.

Chronic heavy alcohol consumption influences the association between genetic variants of GCK or INSR and the development of diabetes in men: A 12-year follow-up study.

Chronic heavy alcohol consumption is a risk factor for diabetes, which is characterized by impaired β-cell function and insulin resistance. We aimed to determine whether the longitudinal associations between genetic variants of glucokinase (GCK) and insulin receptor (INSR) and the risk of developing diabetes were influenced by chronic heavy alcohol consumption. Data were obtained from the Korean Genome and Epidemiology Study.

Tracing diagnosis trajectories over millions of patients reveal an unexpected risk in schizophrenia.

The identification of novel disease associations using big-data for patient care has had limited success. In this study, we created a longitudinal disease network of traced readmissions (disease trajectories), merging data from over 10.4 million inpatients through the Healthcare Cost and Utilization Project, which allowed the representation of disease progression mapping over 300 diseases.

Identification of novel population clusters with different susceptibilities to type 2 diabetes and their impact on the prediction of diabetes.

Type 2 diabetes is one of the subtypes of diabetes. However, previous studies have revealed its heterogeneous features. Here, we hypothesized that there would be heterogeneity in its development, resulting in higher susceptibility in some populations.

COEX-Seq: Convert a Variety of Measurements of Gene Expression in RNA-Seq.

Next generation sequencing (NGS), a high-throughput DNA sequencing technology, is widely used for molecular biological studies. In NGS, RNA-sequencing (RNA-Seq), which is a short-read massively parallel sequencing, is a major quantitative transcriptome tool for different transcriptome studies. To utilize the RNA-Seq data, various quantification and analysis methods have been developed to solve specific research goals, including identification of differentially expressed genes and detection of novel transcripts.

Asymmetric dimethylarginine (ADMA) is identified as a potential biomarker of insulin resistance in skeletal muscle.

To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA).

Mitochondrial DNA copy number augments performance of AC and oral glucose tolerance testing in the prediction of type 2 diabetes.

Here, we tested the performance of the mitochondrial DNA copy number (mtDNA-CN) in predicting future type 2 diabetes (n = 1108). We used the baseline clinical data (age, sex, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure) and the mtDNA-CN, hemoglobin A (AC) levels and results of oral glucose tolerance test (OGTT) including fasting plasma glucose, 1-hour glucose, and 2-hour glucose levels, to predict future diabetes. We built a prediction model using the baseline data and the diabetes status at biannual follow-up of 8 years.

HIA: a genome mapper using hybrid index-based sequence alignment.

Background: A number of alignment tools have been developed to align sequencing reads to the human reference genome. The scale of information from next-generation sequencing (NGS) experiments, however, is increasing rapidly. Recent studies based on NGS technology have routinely produced exome or whole-genome sequences from several hundreds or thousands of samples.

The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children.

Background: Glucokinase regulator (GCKR) plays important roles in the regulation of glucokinase (GK) activity and the metabolism of glucose and lipids. We investigated whether the association between GCKR genetic variants with serum lipids in Korean adults is replicated in children, and whether these genetic influences might be modulated by dietary monounsaturated fatty acid relative to saturated fatty acid (MUFA:SFA) ratio.

Methods: We genotyped 711 children for GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric, biochemical, and dietary measurements.

Replication of Interactions between Genome-Wide Genetic Variants and Body Mass Index in Fasting Glucose and Insulin Levels.

The genetic regulation of glucose and insulin levels might be modified by adiposity. With regard to the genetic factors that are altered by adiposity, a large meta-analysis on the interactions between genetic variants and body mass index with regard to fasting glucose and insulin levels was reported by the Meta-Analyses of Glucose- and Insulin-related trait Consortium (MAGIC), based on European ancestry. Because no replication study has been performed in other ethnic groups, we first examined the link between reported single-nucleotide polymorphisms (SNPs) and fasting glucose and insulin levels in a large Korean cohort (Korean Genome and Epidemiology Study cohort [KoGES], n = 5,814).

Genome-wide association study of metabolic syndrome in koreans.

Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (<5 × 10(-8)), 8 SNPs with genome-wide suggestive p-values (5 × 10(-8) ≤ p < 1 × 10(-5)), and 2 SNPs of more functional variants with borderline p-values (5 × 10(-5) ≤ p < 1 × 10(-4)).

Association between Expression Quantitative Trait Loci and Metabolic Traits in Two Korean Populations.

Most genome-wide association studies consider genes that are located closest to single nucleotide polymorphisms (SNPs) that are highly significant for those studies. However, the significance of the associations between SNPs and candidate genes has not been fully determined. An alternative approach that used SNPs in expression quantitative trait loci (eQTL) was reported previously for Crohn's disease; it was shown that eQTL-based preselection for follow-up studies was a useful approach for identifying risk loci from the results of moderately sized GWAS.

A novel approach for predicting disordered regions in a protein sequence.

Objectives: A number of published predictors are based on various algorithms and disordered protein sequence properties. Although many predictors have been published, the study of protein disordered region prediction is ongoing because different prediction methods can find different disordered regions in a protein sequence.

Methods: Therefore we have used a new approach to find the more varying disordered regions for more efficient and accurate prediction of protein structures.