Metabolomics profiles associated with HbA1c levels in patients with type 2 diabetes.

Glycated hemoglobin (HbA1c) is an indicator of the average blood glucose concentration. Failing to control HbA1c levels can accelerate the development of complications in patients with diabetes. Although metabolite profiles associated with HbA1c level in diabetes patients have been characterized using different platforms, more studies using high-throughput technology will be helpful to identify additional metabolites related to diabetes.

Increased calcium channel in the lamina propria of aging rat.

The alterations of the extracellular matrix (ECM) in lamina propria of the vocal folds are important changes that are associated with decreased vibrations and increased stiffness in aging vocal fold. The aim of this study was to investigate the differences in gene expression of lamina propria using next generation sequencing (NGS) in young and aging rats and to identify genes that affect aging-related ECM changes for developing novel therapeutic target molecule. Among the 40 genes suggested in the NGS analysis, voltage-gated calcium channels (VGCC) subunit alpha1 S (CACNA1S), VGCC auxiliary subunit beta 1 (CACNB1), and VGCC auxiliary subunit gamma 1 (CACNG1) were increased in the lamina propria of the old rats compared to the young rats.

Identification of novel non-synonymous variants associated with type 2 diabetes-related metabolites in Korean population.

Metabolome-genome wide association studies (mGWASs) are useful for understanding the genetic regulation of metabolites in complex diseases, including type 2 diabetes (T2D). Numerous genetic variants associated with T2D-related metabolites have been identified in previous mGWASs; however, these analyses seem to have difficulty in detecting the genetic variants with functional effects. An exome array focussed on potentially functional variants is an alternative platform to obtain insight into the genetics of biochemical conversion processes.

Programmable Nuclease-Based Integration into Novel Extragenic Genomic Safe Harbor Identified from Korean Population-Based CNV Analysis.

Here, we found two genomic safe harbor (GSH) candidates from chromosomes 3 and 8, based on large-scale population-based cohort data from 4,694 Koreans by CNV analysis. Furthermore, estimated genotype of these CNVRs was validated by quantitative real-time PCR, and epidemiological data examined no significant genetic association between diseases or traits and two CNVRs. After screening the GSH candidates by approaches, we designed TALEN pairs to integrate EGFP expression cassette into human cell lines in order to confirm the functionality of GSH candidates in an setting.

Bogotá River anthropogenic contamination alters microbial communities and promotes spread of antibiotic resistance genes.

The increase in antibiotic resistant bacteria has raised global concern regarding the future effectiveness of antibiotics. Human activities that influence microbial communities and environmental resistomes can generate additional risks to human health. In this work, we characterized aquatic microbial communities and their resistomes in samples collected at three sites along the Bogotá River and from wastewaters at three city hospitals, and investigated community profiles and antibiotic resistance genes (ARGs) as a function of anthropogenic contamination.

Predicting stroke and death in patients with heart failure using CHADS-VASc score in Asia.

Background: The CHADS-VASc score is used to assess risk of mortality as well as to stratify risk of stroke in patients with atrial fibrillation (AF). This study evaluated whether CHADS-VASc score was predictive of 1 and 2 year risks of stroke and death in Asian patients with heart failure (HF).

Methods: Patients hospitalized for HF were enrolled in the Korean Acute Heart Failure (KorAHF) registry, a prospective observational multicenter cohort study, between March 2011 and February 2014.

Identification of Dietary Patterns Associated with Incidence of Hyperglycemia in Middle-Aged and Older Korean Adults.

Little is known about the association between dietary patterns and hyperglycemia incidence among Korean adults. Hence, we aimed to prospectively investigate the major dietary patterns associated with hyperglycemia among middle-aged and older Korean adults. In total, 55,457 adults (18,292 men and 37,165 women) aged 40 to 79 years, who were previously enrolled in the Health Examinee Study of the Korean Genome and Epidemiology Study and had no history of type 2 diabetes mellitus (T2DM) or cancer at baseline, were included.

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.

Effects of Inflammation and Depression on Telomere Length in Young Adults in the United States.

Little is known about the associations of inflammation and depression with telomere length. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, the current study assessed the effects of inflammation and depression on telomere length in 1141 young adults in the USA. Depression status was assessed from the World Health Organization Composite International Diagnostic Interview and inflammation status was measured based on C-reactive protein (CRP) concentrations.

Exome chip-driven association study of lipidemia in >14,000 Koreans and evaluation of genetic effect on identified variants between different ethnic groups.

Lipid levels in blood are widely used to diagnose and monitor chronic diseases. It is essential to identify the genetic traits involved in lipid metabolism for understanding chronic diseases. However, the influence of genetic traits varies depending on race, sex, age, and ethnicity.

Dietary inflammatory index is positively associated with serum high-sensitivity C-reactive protein in a Korean adult population.

Objective: To our knowledge, only a few studies have explored the relationship between the inflammatory potential of diet and serum inflammatory markers in Korean adults. The likely novel aim of this study was to examine the association between the dietary inflammatory index (DII) and serum high-sensitivity C-reactive protein (hs-CRP) in a Korean adult population.

Methods: A cross-sectional study was conducted using the data set from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015.

The Korean undiagnosed diseases program: lessons from a one-year pilot project.

Background: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea.

Results: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium.

The association of genetically controlled CpG methylation (cg158269415) of protein tyrosine phosphatase, receptor type N2 (PTPRN2) with childhood obesity.

Protein tyrosine phosphatase, receptor type N2 (PTPRN2) encodes a major islet autoantigen in type-1 diabetes. Previous genetic studies have shown its significant association with obesity. PTPRN2 plays an important role in epigenetic regulation of metabolic diseases and cancers.

Epigenetic analysis in rheumatoid arthritis synoviocytes.

Rheumatoid arthritis (RA) is a complex chronic systematic disease with progressive destruction of the joints by invasive synoviocytes. To characterize the key regulators involved in the development of RA, we obtained multilayer epigenomics data including DNA methylation by whole-genome bisulfite sequencing, miRNA profiles, genetic variations by whole-exome sequencing, and mRNA profiles from synoviocytes of RA and osteoarthritis (OA) patients. The overall DNA methylation patterns were not much different between RA and OA, but 523 low-methylated regions (LMRs) were specific to RA.

Gene-environment interactions related to blood pressure traits in two community-based Korean cohorts.

Hypertension is a complex disorder caused by genetic and environmental risk factors. Recently, genome-wide association studies (GWASs) identified more than 100 genetic variants for blood pressure traits and hypertension. However, the interactions between these genetic variants and environmental factors have not been systematically investigated.

The genetic and epigenetic association of LDL Receptor Related Protein 1B (LRP1B) gene with childhood obesity.

Low-density lipoprotein Receptor Related Protein 1B (LRP1B) is homologous to the gigantic lipoprotein receptor-related protein 1 that belongs to the family of Low-density lipoprotein receptors. Previous genetic association studies of the LRP1B gene have shown its genetic association with obesity. Through exome sequencing of the LRP1B gene from a childhood severe obesity cohort (n = 692), we found novel single nucleotide polymorphism (rs431809) in intron 4, which has been significantly correlated with both body mass index (BMI) and waist-hip-ratio (WHR).

The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits.

We introduce the design and implementation of a new array, the Korea Biobank Array (referred to as KoreanChip), optimized for the Korean population and demonstrate findings from GWAS of blood biochemical traits. KoreanChip comprised >833,000 markers including >247,000 rare-frequency or functional variants estimated from >2,500 sequencing data in Koreans. Of the 833 K markers, 208 K functional markers were directly genotyped.

Efficient test-based variable selection for high-dimensional linear models.

Variable selection plays a fundamental role in high-dimensional data analysis. Various methods have been developed for variable selection in recent years. Well-known examples are forward stepwise regression (FSR) and least angle regression (LARS), among others.

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.

Oropouche orthobunyavirus: Genetic characterization of full-length genomes and development of molecular methods to discriminate natural reassortments.

Oropouche orthobunyavirus (OROV) has significant impact in public health in Amazon region. This arbovirus is one of the most common causes of febrile illness in Brazil, and is responsible for several epidemics since 1960's. In this study, we sequenced and characterized the complete coding sequences (S-, M- and L-RNA) of 35 OROV isolates from Brazil.

Interethnic analyses of blood pressure loci in populations of East Asian and European descent.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model.

Multiple genotype-phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population.

Background: Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test.

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.

We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

Genome-wide methylation analysis identifies ELOVL5 as an epigenetic biomarker for the risk of type 2 diabetes mellitus.

Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites.