Search Results (22)

Chronic lymphocytic leukemia (CLL) is uncommon in Asia, and longitudinal genomic data from Asian cohorts are limited. We conducted serial whole-exome sequencing (WES) in a multicenter Korean cohort of newly diagnosed, elderly CLL treated with chlorambucil–obinutuzumab to evaluate mutational heterogeneity and clonal hematopoiesis of indeterminate potential (CHIP) during treatment and follow-up. Tumor-only variants were filtered, restricted to nonsynonymous or loss-of-function coding/splice-site mutations, and summarized as a binary patient-by-gene matrix for principal component analysis (PCA), trajectory analysis, and k-means clustering. CHIP was defined as ≥1 qualifying mutation in a prespecified CHIP gene set. Baseline PCA was more compact in patients with complete response at end of treatment, whereas partial response or progressive disease cases were more dispersed. PCA trajectories were compact and directionally consistent in complete responders, more dispersed in partial responders, and highly heterogeneous without a dominant direction in progressive disease. Clustering identified dispersed and compact clusters, and CHIP-associated mutations were enriched in the dispersed cluster (55.6% vs. 8.3%, Fisher’s exact p = 0.0086). In paired samples collected 3–5 months after end of treatment, CHIP status changed in some patients. Serial WES may provide complementary information to treatment response, although these observations require confirmation in larger cohorts. Full article

Background/Objectives: Alzheimer’s disease (AD) exhibits high heritability (60–80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean Chip v2.0 genotyping (~1.2 M SNPs) and Illumina EPICv2 DNA methylation profiling. Genetic burden score (GBS) was calculated by summing risk alleles across 320 variants in six AD-associated genes (APOE, PICALM, CLU, CR1, BIN1, and ABCA7). Results: An unexpected pattern was observed in this family: the affected individual (J-003) had the lowest GBS (39 alleles), while individuals with higher genetic burden (51–61 alleles) remained cognitively healthy. J-003 also exhibited lower APOE methylation (β = 0.495) compared to the family mean (β = 0.523). CR1 contributed the most risk alleles across the family, followed by PICALM. Conclusions: This single-case observation cannot establish causality, generalizability, or biological significance. The affected individual’s lower APOE methylation may represent a causal factor, disease consequence, or coincidental variation—scenarios that cannot be distinguished from this dataset. Validation in larger cohorts with multiple affected individuals is required to determine whether integrated multi-omics approaches can inform personalized risk assessment in familial contexts. Full article

Background: Osteoporosis is highly prevalent in postmenopausal women, yet genome-wide association studies often miss disease-relevant variants because of incomplete single nucleotide polymorphism (SNP) coverage and platform-specific limitations. We aimed to identify genetic contributors to osteoporosis risk by integrating two exome-based genotyping platforms with multilayer analytic approaches. Methods: We analyzed extreme osteoporosis phenotypes in Korean postmenopausal women from the Korean Genome and Epidemiology Study (KoGES) Ansan–Anseong cohorts using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. After standard quality control, single-SNP logistic regression, cross-platform overlap analysis, and three machine-learning models were applied. Predicted functional impact was evaluated using multiple in silico algorithms and conservation scores. Finally, datasets from both platforms were merged, and cross-platform linkage disequilibrium (LD) blocks were defined to identify loci containing SNPs with p < 1 × 10⁻⁴. Results: No overlapped SNP reached genome-wide significance, but rs2076212 in PNPLA3 achieved suggestive significance (p < 1 × 10⁻⁵) only on the Illumina array. Cross-platform analysis identified 111 overlapping SNPs in 70 genes. Integrated machine-learning, in silico, and conservation evidence prioritized ARMS2, CCDC92, NQO1, ZNF510, PTPRB, and DYNC2H1 as candidate genes. LD-block analysis revealed 10 blocks with at least one SNP at p < 1 × 10⁻⁴, including four chromosome 12 loci (NAV2, BICD1, CCDC92, ZNF664) that became apparent only when LD patterns were evaluated jointly across platforms. Conclusions: Combining dual exome arrays with LD-block analysis, machine learning, and functional prediction improved sensitivity for detecting low bone mineral density-related loci and highlighted CCDC92, DYNC2H1, NQO1, and related genes as biologically plausible candidates for future validation. Full article

Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE p ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis (p < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency (p < 0.01). Several of these genes were implicated in bone metabolism (e.g., ESRRG, PECAM1, COL6A5), vitamin D metabolism (e.g., NADSYN1, EFTUD1), skeletal muscle function (e.g., PACSIN2, ESRRG), and reproductive processes (e.g., CPEB1, EFCAB6, ASXL3). Notably, the CPEB1 rs783540 SNP exhibited the strongest association (p < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle–bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms. Full article

Korea has a high population density, considering the size of its territory. Therefore, the importance of convenient and comfortable apartment buildings and high-rise residential–commercial complex buildings has been rising. In addition, because of the improvement in the standard of living along with continuous national economic growth, the interest in well-being and the expectation of a quiet life with a comfortable and pleasant residential environment have also been increasing. However, Koreans have a lifestyle involving sitting on the floor, so floor impact noise has been occurring more and more frequently. Because of this, neighborly disputes have been a serious social problem. And lately, damage and disputes from noise between floors have been increasing much more. The present work, therefore, used waste tire chips as a resilient material for reducing floor impact noise in order to recycle waste tires effectively. Also, a compounded resilient material, which combines EPS (expanded polystyrene), a flat resilient material on the upper part, with waste tire chips for the lower part, was developed. After constructing waste tire chips at a standardized test building, experiments with both light-weight and heavy-weight floor impact noise were performed. The tests confirmed that waste tire chips, when used as a resilient material, can effectively reduce both light-weight and heavy-weight floor impact noise. Full article

Background: Understanding gene–diet interactions is crucial for establishing dietary guidelines for cardiovascular diseases (CVD). This study analyzed the interaction between dietary intake and six genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNP) associated with high-density lipoprotein (HDL) cholesterol levels and their impact on CVD risk. Methods: A total of 68,806 participants in the Korean Genome and Epidemiology Study (KoGES) were analyzed. Six target SNPs (LPL: rs17482753; ABCA1: rs1883025; APOA5: rs651821; LIPC: rs1077835; CETP: rs17231506; and LIPG: rs9953437) were extracted from genome-wide SNP genotype data. Dietary intake was assessed using a food frequency questionnaire. SNP genotyping was conducted using the Korea Biobank Array (Korean Chip), a specialized genotyping platform designed for GWAS of blood biochemical traits in the Korean population. SNP–diet interactions on CVD risk were analyzed using generalized linear models (GLM). Results: Among the six SNPs, ABCA1: rs1883025 and APOA5: rs651821 showed significant gene–diet interactions. For rs1883025 (ABCA1), carriers of the T allele exhibited reduced HDL cholesterol levels. However, in the high-protein intake group, individuals with the T/T genotype had a significantly lower risk of ischemic stroke compared to those in the low-protein intake group (interaction p-value = 0.044). For rs651821 (APOA5), carriers of the T allele also had lower HDL cholesterol levels, but individuals with the C/C genotype (wild-type homozygotes) in the low-fat intake group showed a significantly reduced risk of coronary artery disease (interaction p-value = 0.0155). Conclusions: This study suggests potential interactions between polymorphisms associated with low HDL cholesterol and dietary patterns, particularly high-protein and low-fat diets, in relation to CVD risk. These findings highlight the importance of personalized dietary recommendations based on genetic profiles to reduce CVD risk. They provide a basis for future research aimed at developing precision nutrition guidelines and targeted interventions to manage hypo-HDL cholesterolemia and nutrition-related CVD risks. Full article

High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic inflammation and is associated with developing dyslipidemia. However, the causality between hs-CRP and dyslipidemia remains unresolved. This study aimed to investigate the relationship between hs-CRP concentrations and dyslipidemia and to explore the potential causal link using Mendelian randomization (MR) analysis. A nested case–control study was conducted with 1174 participants, and genotype data were analyzed using the Korean Chip. A genome-wide association study (GWAS) identified rs76400217 as a suitable instrumental variable (IV) due to its significant association with hs-CRP (p < 10⁻⁸). Logistic regression models, adjusted for confounders, were used to evaluate the association between hs-CRP and dyslipidemia. An MR analysis was performed using a two-stage least squares (2SLS) method, with rs76400217 as the IV to assess causality. Logistic regression showed a significant association between hs-CRP concentrations and dyslipidemia (OR 2.08, 95% CI: 1.81–2.39, p < 0.001). This association remained significant after adjusting for factors such as age, sex, alcohol consumption, and BMI. The MR analysis using rs76400217 as the IV confirmed the strong associations with hs-CRP concentrations (p < 0.001) in all models, but the causality between hs-CRP and dyslipidemia was not statistically significant. Thus, no evidence of a causal relationship between hs-CRP and the risk of dyslipidemia was found in the Korean population. The strong association observed between hs-CRP and dyslipidemia may be due to other contributing factors rather than a direct cause. Full article

The purpose of this study was to estimate the homozygosity distribution and compute genomic and conventional inbreeding coefficients in three genetically diverse pig breed populations. The genomic and pedigree data of Duroc (1586), Landrace (2256), and Yorkshire (3646) were analyzed. We estimated and compared various genomic and pedigree inbreeding coefficients using different models and approaches. A total of 709,384 ROH segments in Duroc, 816,898 in Landrace, and 1,401,781 in Yorkshire, with average lengths of 53.59 Mb, 56.21 Mb, and 53.46 Mb, respectively, were identified. Relatively, the Yorkshire breed had the shortest ROH segments, whereas the Landrace breed had the longest mean ROH segments. Sus scrofa chromosome 1 (SSC1) had the highest chromosomal coverage by ROH across all breeds. Across breeds, an absolute correlation (1.0) was seen between F_ROH total and F_ROH1–2Mb, showing that short ROH were the primary contributors to overall F_ROH values. The overall association between genomic and conventional inbreeding was weak, with values ranging from 0.058 to 0.140. In contrast, total genomic inbreeding (F_ROH) and ROH classes showed a strong association, ranging from 0.663 to 1.00, across the genotypes. The results of genomic and conventional inbreeding estimates improve our understanding of the genetic diversity among genotypes. Full article

Our previous study suggested that the Mono-ADP ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism is significantly associated with white blood cell (WBC) count in the Korean population. The present study aimed to evaluate the clinical relevance of the MACROD2 rs6110695 A>G polymorphism for predicting WBC count by utilizing plasma metabolites and a single-nucleotide polymorphism (SNP). Two groups were characterized by MACROD2 rs6110695 A>G SNP genotypes among 139 healthy subjects based on the genetic information provided in our previous work: rs6110695 AA genotype group (n = 129) and rs6110695 AG genotype group (n = 10). Plasma global metabolic profiling was performed using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). To estimate the predictive abilities of WBC count models using the rs6110695 genotype and/or significant differential metabolites, multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were conducted. The AG genotype had greater WBC-to-apolipoprotein (apo) A-I ratios; counts of WBCs, lymphocytes, monocytes, and granulocytes; monocyte-to-lymphocyte ratio (MLR); and monocyte-to-platelet ratio (MPR) than the AA genotype. In terms of metabolic profile, indoleacetic acid, and butyrylcarnitine levels were considerably distinct between the two groups, and these metabolites were considered to be meaningful prognostic variables for the rs6110695 genotype. Finally, ROC curve analysis demonstrated that the model containing the rs6110695 genotype and the two main metabolites was reliable. The present study revealed that individuals carrying the rs6110695 AG genotype with high plasma indoleacrylic acid and butyrylcarnitine levels might have elevated WBC counts. The rs6110695 genotype and the concentrations of indoleacrylic acid and butyrylcarnitine could contribute to reducing the risk of chronic diseases in the future. Full article

16p11.2 copy number variations (CNVs) are increasingly recognized as one of the most frequent genomic disorders, and the 16p11.2 microdeletion exhibits broad phenotypic variability and a diverse clinical phenotype. We describe the neurodevelopmental course and discordant clinical phenotypes observed within and between individuals with identical 16p11.2 microdeletions. An analysis with the CytoScan Dx Assay was conducted on a GeneChip System 3000Dx, and the sample signals were then compared to a reference set using the Chromosome Analysis Suite software version 3.1. Ten patients from six separate families were identified with 16p11.2 microdeletions. Nine breakpoints (BPs) 4-5 and one BP2-5 of the 16p11.2 microdeletion were identified. All patients with 16p11.2 microdeletions exhibited developmental delay and/or intellectual disability. Sixty percent of patients presented with neonatal hypotonia, but muscle weakness improved with age. Benign infantile epilepsy manifested between the ages of 7–10 months (a median of 8 months) in six patients (60%). Vertebral dysplasia was observed in two patients (20%), and mild scoliosis was noted in three patients. Sixty percent of patients were overweight. We present six unrelated Korean families, among which identical 16p11.2 microdeletions resulted in diverse developmental trajectories and discordant phenotypes. The clinical variability and incomplete penetrance observed in individuals with 16p11.2 microdeletions remain unclear, posing challenges to accurate clinical interpretation and diagnosis. Full article

The objective of this study was to identify quantitative trait loci (QTL) and nearby candidate genes that influence body conformation traits. Phenotypic data for 24 body conformation traits were collected from a population of 2329 Korean Holstein cattle, and all animals were genotyped using the 50 K Illumina bovine SNP chip. A total of 24 genome-wide significant SNPs associated with 24 body conformation traits were identified by genome-wide association analysis. The selection of the most promising candidate genes was based on gene ontology (GO) terms and the previously identified functions that influence various body conformation traits as determined in our study. These genes include KCNA1, RYBP, PTH1R, TMIE, and GNAI3 for body traits; ANGPT1 for rump traits; MALRD1, INHBA, and HOXA13 for feet and leg traits; and CDK1, RHOBTB1, and SLC17A1 for udder traits, respectively. These findings contribute to our understanding of the genetic basis of body conformation traits in this population and pave the way for future breeding strategies aimed at enhancing desirable traits in dairy cattle. Full article

Metabolic syndrome (MetS) is a complex condition of metabolic disorders and shows a steady onset globally. Ceramides are known as intracellular signaling molecules that influence key metabolism through various pathways such as MetS and insulin resistance. Therefore, it is important to identify novel genetic factors related to increased plasma ceramides in subjects with MetS. Here we first measured plasma ceramides levels in 37 subjects with MetS and in 38 healthy subjects by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, levels of C16 ceramide (Cer-16), C18 ceramide (Cer-18), C20 ceramide (Cer-20), C18 dihydroceramide (DhCer-18), C24 dihydroceramide (DhCer-24), and C24:1 dihydroceramide (DhCer-24:1) were significantly increased in MetS group (p < 5.0 × 10⁻²). We then performed single nucleotide polymorphism (SNP) genotyping to identify variants associated with elevated plasma ceramides in MetS group using Axiom^® Korea Biobank Array v1.1 chip. We also performed linear regression analysis on genetic variants involved in ceramide synthesis and significantly elevated plasma ceramides and dihydroceramides. Ten variants (rs75397325, rs4246316, rs80165332, rs62106618, rs12358192, rs11006229, rs10826014, rs149162405, rs6109681, and rs3906631) across six genes (ACER1, CERS3, CERS6, SGMS1, SPTLC2, and SPTLC3) functionally involved in ceramide biosynthesis showed significant associations with the elevated levels of at least one of the ceramide species in MetS group at a statistically significant threshold of false discovery rate (FDR)-adjusted p < 5.0 × 10⁻². Our findings suggest that the variants may be genetic determinants associated with increased plasma ceramides in individuals with MetS. Full article

Lactic acid bacteria biofilms can be used to reduce foodborne pathogen contamination in the food industry. However, studies on growth inhibition of foodborne pathogens by inducing biofilm formation of antagonistic microorganisms on abiotic surfaces are rare. We developed a desiccation-tolerant antimicrobial probiotic biofilm. Lactobacillus sakei M129-1 and Pediococcus pentosaceus M132-2 isolated from fermented Korean foods were found to exhibit broad-spectrum antibacterial activity against Bacillus cereus, Escherichia coli O157:H7, Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica. Their biofilm levels were significantly (p < 0.05) higher on stainless steel than on polyethylene or ceramic. Biofilms of both isolates showed significantly (p < 0.05) enhanced resistance against desiccation (exposure to 43% atmospheric relative humidity) as compared with the isolates not in the biofilm form. The antimicrobial activity of the isolates was sustained in dried biofilms on stainless steel surface; the initial number of foodborne pathogens (average 7.0 log CFU/mL), inoculated on stainless steel chips containing L. sakei M129-1 or P. pentosaceus M132-2 biofilm decreased to less than 1.0 log CFU within 48 h. The lactic acid bacteria antibacterial biofilms developed in this study may be applied to desiccated environmental surfaces in food-related environments to improve microbiological food safety. Full article

Recently, the Korean government has announced a plan to develop a satellite-based navigation system called the Korean Positioning System (KPS). When designing a new Radio Navigation Satellite Service (RNSS) signal, the use of the S-band has emerged as an alternative to avoiding signal congestion in the L-bands, and South Korea is considering using the S-band with the L-bands. Therefore, this study proposed possible S-band signal candidates and evaluated their performance, such as the radio frequency (RF) compatibility, spectral efficiency, ranging performance, and receiver complexity. Several figures-of-merit (FoMs) were introduced for quantitative performance evaluation for each candidate. Each FoM was calculated using an analytical equation by considering the signal design parameters, such as the center frequency, modulation scheme, and chip rate. The results showed that the outstanding candidate signal was different depending on the signal performance of interest and the reception environments. Therefore, we discuss and summarize the signal performance analysis results considering the whole FoMs together. Under the assumptions given in this paper, the binary phase shift keying (BPSK)(1), sine-phased binary offset carrier (BOC_s)(5,2), and BPSK signals were superior for the spectral efficiency, ranging performance, and receiver complexity, respectively. Full article

Particulate matter with a diameter of ≤10 µm (PM₁₀) and nitrogen dioxide (NO₂) affect the DNA methylation in the fetus, but epigenetic studies regarding prenatal exposure to air pollution in Asia are lacking. Therefore, this study aimed to assess whether there is any association between the ambient concentrations of PM₁₀ and NO₂ and CpG methylation in the cord blood DNA by using a Korean birth cohort. The concentrations of the air pollutants were incorporated into the final LUR model by using the maternal address data. The methylation level was determined using HumanMethylationEPIC BeadChip and a linear regression analysis model. A multipollutant model including both PM₁₀ and NO₂ and models with single pollutants were used for each trimester exposure. The number of differentially methylated positions was the largest for midpregnancy exposure in both the single pollutant models and the multipollutant regression analysis. Additionally, gene-set analysis regarding midpregnancy exposure revealed four gene ontology terms (cellular response to staurosporine, positive regulation of cytoskeleton organization, neurotransmitter transport, and execution phase of apoptosis). In conclusion, these findings show an association between prenatal PM₁₀ and NO₂ exposure and DNA methylation in several CpG sites in cord blood cells, especially for midpregnancy exposure. Full article