Korean Genome And Epidemiology Study Research Articles

Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism.

Hypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES). Participants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL (n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (<40 mg/dL for men and < 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters. The participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely ZPR1_rs3741297, CETP_rs708272, BUD13_rs180327, and ALDH1A2_rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with p < 5×10-8. The risk alleles of CETP_rs708272 and ALDH1A2_rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status. Adults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk.

Frequency of actionable secondary findings in 7472 Korean genomes derived from the National Project of Bio Big Data pilot study.

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.

Longitudinal trajectories of atherogenic index of plasma and risks of cardiovascular diseases: results from the Korean genome and epidemiology study

BackgroundAlthough the atherogenic index of plasma (AIP) based on a single measurement is a known risk factor for cardiovascular disease (CVD), little is known about whether changes in AIP over time are related to incident CVD. We aimed to determine whether AIP trajectory, which reflects homogenous AIP trends for a particular period, is associated with CVD risk.MethodsData from 5,843 participants of the Korean Genome and Epidemiology Study (KoGES) were analyzed. The KoGES had been conducted biennially from the baseline survey (2001–2002) to the eighth follow-up survey (2017–2018). The research design specifies the exposure period from baseline to the third follow-up, designates the latent period at the fourth follow-up, and establishes the event accrual period from the fifth to the eighth follow-up. During the exposure period, we identified two trajectories: a decreasing (n = 3,036) and an increasing group (n = 2,807) using latent variable mixture modeling. Information on CVD was collected initially through the self-reporting, followed by in depth person-to-person interview conducted by a well-trained examiner. During the event accrual period, the cumulative incidence rates of CVD between the two AIP trajectory groups were estimated using Kaplan–Meier analysis with the log-rank test. Multiple Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsThe increasing AIP trajectory group had a significantly higher cumulative incidence rate of CVD than the decreasing AIP trajectory group. Compared to the decreasing AIP trajectory group, the increasing AIP trajectory group had a higher risk of incident CVD (HR: 1.31, 95% CI: 1.02–1.69) after adjusting for confounders.ConclusionsThe risk of incident CVD increased when the AIP level showed an increasing trend and remained high over a long period. This suggests that checking and managing the trajectory of the AIP can be a preventive strategy for incident CVD.

Relationship between DNA methylation changes and skeletal muscle mass

BackgroundSarcopenia is a disease diagnosed in the elderly. In patients with sarcopenia, the muscle mass decreases every year. The occurrence of sarcopenia is greatly affected by extrinsic factors such as eating habits, exercise, and lifestyle. The present study aimed to determine the relationship between muscle mass traits and genes affected by epigenetic factors with three different adjustment methods using Korean Genome and Epidemiology Study (KOGES) data.ResultsWe conducted a demographic study and DNA methylation profiling by three studies according to the muscle mass index (MMI) adjustment methods: appendicular skeletal muscle mass divided by body weight (MMI1); appendicular skeletal muscle mass divided by square of height (MMI2); appendicular skeletal muscle mass divided by BMI (MMI3). We analyzed differentially methylated regions (DMRs) for each group. We then restricted our subjects to be top 30% (T30) and bottom 30% (B30) based on each MMI adjustment method. Additionally, we performed enrichment analysis using PathfindR to evaluate the relationship between identified DMRs and sarcopenia. A total of 895 subjects were included in the demographic study. The values of BMI, waist, and hip showed a significant difference in all three groups. Among 446 participants, 44 subjects whose DNA methylation profiles were investigated were included for DNA methylation analysis. The results of enrichment analysis showed differences between groups. In the women group through MMI1 method, only the glutamatergic synapse pathway showed a significant result. In the men group through MMI2 method, the adherens junction pathway was the most significant. Women group through MMI2 method showed similar results, having an enriched Rap1 signaling pathway. In men group through MMI3 method, the Fc epsilon RI signaling pathway was the most enriched. Particularly, the notch signaling pathway was significantly enriched in women group through MMI3 method.ConclusionThis study presents results about which factor should be concerned first in muscle mass index (MMI) adjustment. The present study suggested that GAB2 and JPH3 in MMI1 method, HLA-DQB1 and TBCD in MMI2 method, GAB2, NDUFB4 and ISPD in MMI3 method are potential genes that can have an impact on muscle mass. It could enable future epigenetic studies of genes based on annotation results. The present study is a nationwide study in Korea with the largest size up to date that compares adjustment indices for MMI in epigenetic research.

Oxidative balance score inversely associated with the prevalence and incidence of metabolic syndrome: analysis of two studies of the Korean population.

Pro-oxidant/antioxidant imbalances leading to chronic inflammation and insulin resistance can contribute to the development of metabolic syndrome (MetS). Oxidative Balance Score (OBS), a comprehensive measure of exposure to pro- and anti-oxidants, represents an individual's total oxidative balance. This study aimed to evaluate the association between OBS and MetS using two large datasets. We analyzed data from 2,735 adults older than 19 years from the 2021 Korean National Health and Nutritional Examination Survey (KNHANES) and 5,807 adults aged 40-69 years from the Korean Genome and Epidemiology Study (KoGES). In each dataset, OBS was categorized into sex-specific tertiles (T). In KNHANES, the odds ratios and 95% confidence intervals for prevalent MetS in T3, compared to T1, were 0.44 (0.29-0.65) in men and 0.34 (0.23-0.50) in women after adjusting for confounders. In KoGES, the hazard ratios and 95% confidence intervals for incident MetS in T3, compared to T1, were 0.56 (0.48-0.65) in men and 0.63 (0.55-0.73) in women after adjusting for confounders. OBS appears to be inversely related to MetS, which suggests that adopting lifestyle behaviors that decrease oxidative stress could be an important preventive strategy for MetS.

Sex-specific associations of γ-glutamyltransferase to HDL-cholesterol ratio and the incident risk of cardiovascular disease: three Korean longitudinal cohorts from different regions.

The combination of gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) (GGT/HDL-C) is a novel noninsulin-based marker for assessing the risk of nonalcoholic fatty liver disease and type 2 diabetes mellitus. However, whether the GGT/HDL-C ratio is related to the risk of incident cardiovascular disease (CVD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of GGT/HDL-C ratio on incident CVD risk in three large cohorts of Korean men and women. Data were assessed from 27,643 participants without CVD from the Korean Genome and Epidemiology Study (KoGES), Health Risk Assessment Study (HERAS), and Korea Health Insurance Review and Assessment (HIRA) (HERAS-HIRA) datasets. The participants were divided into four groups according to the GGT/HDL-C quartiles. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD using multivariate Cox proportional-hazard regression models over a 50-month period following the baseline survey. During the follow-up period, 949 patients (3.4%; 529 men and 420 women) developed CVD. The HRs of CVD for GGT/HDL-C quartiles 2-4 were 1.36 (95% CI, 0.91-2.02), 1.54 (95% CI, 1.05-2.26), and 1.66 (95% CI, 1.12-2.47) after adjusting for metabolic parameters in women, but GGT/HDL-C did not show a trend toward increases in incident CVD in men. Regional discrepancies were evident in the results; the increase in HR in the metropolitan hospital cohort was more pronounced than that in the urban cohort, and the risk was not increased in the rural cohort. GGT/HDL-C ratio may be a useful predictive marker for CVD in women. Furthermore, the prevalence of CVD was strongly correlated with the GGT/HDL-C ratio in metropolitan areas, and this correlation was more significant than that observed with GGT or HDL-C in isolation.

Elevated Uric Acid Levels with Early Chronic Kidney Disease as an Indicator of New-Onset Ischemic Heart Disease: A Cohort of Koreans without Diabetes.

Several studies have showed that hyperuricemia is related to the development of ischemic heart disease (IHD). There is also growing evidence indicating that hyperuricemia may contribute to the progression of IHD as a pathogenic factor. Ironically, uric acid can be an antioxidant agent, as shown in experimental studies. The aim of our study is to analyse the association between uric acid and IHD with early-stage chronic kidney disease (CKD). Data were assessed from 17,492 participants without cardiovascular disease from the Korean Genome and Epidemiology Study (KoGES) and Korea Health Insurance Review and Assessment (HIRA) data. The subjects were categorized as four groups according to CKD and uric acid levels. We retrospectively evaluated hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD by using multivariate Cox regression analysis over a 4-year period from the baseline survey. During the follow-up, 335 individuals (3.4%; 236 men and 99 women) developed IHD. Compared to the participants without elevated uric acid and early CKD HRs for incident IHD according to uric acid levels and early CKD, the uric acid level was 1.13 (95% CI, 0.86-1.48) in participants with elevated uric acid and without early CKD, 0.99 (95% CI, 0.55-1.77) in participants without elevated uric acid and with early CKD, and 1.65 (95% CI, 1.03-2.66) in participants with elevated uric acid and early CKD after adjusting for confounding metabolic factors. Early CKD and high uric acid levels increased the risk of new-onset IHD (HR, 1.65; 95% CI, 1.03-2.66). Elevated uric acid levels were related to an increased risk of incident IHD in early-stage CKD patients. It is expected that uric acid can be a reliable predictor for IHD, even in early-stage CKD patients; thus, in those with CKD, proactively managing uric acid levels can play a significant role in reducing the risk of cardiovascular disease.

The Effect of DNA Methylation in the Development and Progression of Chronic Kidney Disease in the General Population: An Epigenome-Wide Association Study Using the Korean Genome and Epidemiology Study Database.

Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development. We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m2 at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period ("CKD prediction" analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years ("kidney function slope" analysis). In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, NPHS2, CHCHD4, and AHR, were found to be significant in the CKD prediction analysis and related to a decline in kidney function. It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function.

Development of a Polygenic Risk Score for BMI to Assess the Genetic Susceptibility to Obesity and Related Diseases in the Korean Population.

Hundreds of genetic variants for body mass index (BMI) have been identified from numerous genome-wide association studies (GWAS) in different ethnicities. In this study, we aimed to develop a polygenic risk score (PRS) for BMI for predicting susceptibility to obesity and related traits in the Korean population. For this purpose, we obtained base data resulting from a GWAS on BMI using 57,110 HEXA study subjects from the Korean Genome and Epidemiology Study (KoGES). Subsequently, we calculated PRSs in 13,504 target subjects from the KARE and CAVAS studies of KoGES using the PRSice-2 software. The best-fit PRS for BMI (PRSBMI) comprising 53,341 SNPs was selected at a p-value threshold of 0.064, at which the model fit had the greatest R2 score. The PRSBMI was tested for its association with obesity-related quantitative traits and diseases in the target dataset. Linear regression analyses demonstrated significant associations of PRSBMI with BMI, blood pressure, and lipid traits. Logistic regression analyses revealed significant associations of PRSBMI with obesity, hypertension, and hypo-HDL cholesterolemia. We observed about 2-fold, 1.1-fold, and 1.2-fold risk for obesity, hypertension, and hypo-HDL cholesterolemia, respectively, in the highest-risk group in comparison to the lowest-risk group of PRSBMI in the test population. We further detected approximately 26.0%, 2.8%, and 3.9% differences in prevalence between the highest and lowest risk groups for obesity, hypertension, and hypo-HDL cholesterolemia, respectively. To predict the incidence of obesity and related diseases, we applied PRSBMI to the 16-year follow-up data of the KARE study. Kaplan-Meier survival analysis showed that the higher the PRSBMI, the higher the incidence of dyslipidemia and hypo-HDL cholesterolemia. Taken together, this study demonstrated that a PRS developed for BMI may be a valuable indicator to assess the risk of obesity and related diseases in the Korean population.

All-cause and major-cause mortality associated with sleep latency in the Korean Genome and Epidemiology Study (KoGES): a population-based prospective cohort study

The all-cause and cause-specific mortality risk associated with sleep latencies in the general adult population is unknown. We aimed to investigate the association of habitual prolonged sleep latency with long-term all-cause and cause-specific mortality in adults. The Korean Genome and Epidemiology Study (KoGES) is a population-based prospective cohort study comprising community-dwelling men and women aged 40-69 years from Ansan, South Korea. The cohort was studied bi-annually from April 17, 2003, to Dec 15, 2020, and the current analysis included all individuals who completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire between April 17, 2003, and Feb 23, 2005. The final study population comprised 3757 participants. Data were analysed from Aug 1, 2021, to May 31, 2022. The main exposure was sleep latency groups based on the PSQI questionnaire: fell asleep in 15 min or less, fell asleep in 16-30 min, occasional prolonged sleep latency (fell asleep in >30 min once or twice a week in the past month) and habitual prolonged sleep latency (fell asleep in >60 min more than once a week or fell asleep in >30 min ≥3 times a week, or both) in the past month at baseline. Outcomes were all-cause and cause-specific (cancer, cardiovascular disease, and other causes) mortality reported during the 18-year study period. Cox proportional hazards regression models were used to examine the prospective relationship between sleep latency and all-cause mortality, and competing risk analyses were done to investigate the association of sleep latency with cause-specific mortality. During a median follow-up of 16·7 years (IQR 16·3-17·4), 226 deaths were reported. After adjusting for demographic characteristics, physical characteristics, lifestyle factors, chronic conditions, and sleep variables, self-reported habitual prolonged sleep latency was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2·22, 95% CI 1·38-3·57) compared to the reference group (those who fell asleep in 16-30 min). In the fully adjusted model, habitual prolonged sleep latency was associated with a more than doubled risk of dying from cancer compared to the reference group (HR 2·74, 95% CI 1·29-5·82). No significant association was observed between habitual prolonged sleep latency and deaths from cardiovascular disease and other causes. In this population-based prospective cohort study, habitual prolonged sleep latency was independently associated with an increased risk of all-cause and cancer-specific mortality in adults (independently of demographic characteristics, lifestyle factors, chronic morbidities, and other sleep variables). Although further studies are warranted to investigate the causality of the relationship, strategies or interventions to prevent habitual prolonged sleep latencies might enhance longevity in the general adult population. Korea Centers for Disease Control and Prevention.

Association of Fried Food Intake with Gastric Cancer Risk: A Systemic Review and Meta-Analysis of Case-Control Studies.

Gastric cancer is one of the most prevalent cancers in Asia, and has a significant global incidence. However, the impact of fried food consumption on gastric cancer risk remains uncertain, mainly due to the limited number of participants in previous studies. To address this knowledge gap, we aimed to examine the association between fried food intake and gastric cancer incidence through a comprehensive meta-analysis. We conducted a thorough search across multiple databases, including PubMed, EMBASE, Google Scholar, Cochrane Library, China National Knowledge Infrastructure (CNKI), Korean Information Service System (KISS), and Research Information Service System (RISS), to collect studies. The newly analyzed results of the Korean Genome and Epidemiology Study (KoGES) findings were added. We assessed integrated odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) from the selected studies using Cochrane RevMan 5.0 for the meta-analysis. The quality of the studies included in the meta-analysis was assessed using the Study Quality Assessment Tool of the National Heart, Lung, and Blood Institute (NHLBI). We included 18 studies in the analysis, which compared the impact of fried food intake in gastric cancer patients (n = 5739) and healthy adults (control, n = 70,933). There was a significant positive association between gastric cancer risk and fried food intake (OR = 1.52, 95% CI = 1.23-1.87, I2 = 76%, p = 0.0001). The relationship was found to be significant in both non-East Asians (OR = 1.48, 95% CI = 1.18-1.85, I2 = 31%, p = 0.0006) and East Asians (OR = 1.54, 95% CI = 1.14-2.08, I2 = 83%, p = 0.005). In conclusion, this meta-analysis supports the notion that fried food intake is associated with an increased risk of gastric cancer in both non-Asians and Asians. Promoting a reduction in fried food consumption as a measure against gastric cancer risk is recommended.

Effect of physical activity on the change in carotid intima-media thickness: An 8-year prospective cohort study.

There is a demand for longitudinal studies that use both objective and subjective measures of physical activity to investigate the association of physical activity with the change in carotid intima-media thickness (CIMT). In order to investigate such association, we conducted an 8-year follow-up study that used both objective and subjective measures of physical activity. This cohort study used subsamples of the ongoing Korean Genome and Epidemiology Study (KoGES). Included participants were between 49 to 79 years of age at baseline. Exclusion criteria included incomplete assessments of pedometer/accelerometer, international physical activity questionnaire (IPAQ), and baseline CIMT. Participants with a history of cardiovascular diseases were further excluded. Linear regression models were used for the main analysis. Age differences were assessed by stratifying the participants into < 60 years and ≥ 60 years. After removing excluded participants, 835 participants were included in the final analysis (age, 59.84 ± 6.53 years; 326 (39.04%) males). 453 participants were < 60 years and 382 participants were ≥ 60 years. The daily total step count was inversely associated with the percent change in overall CIMT over 8-years (β = -0.015, standard error = 0.007, P = 0.034). This association was present among participants in the < 60-year-old group (β = -0.026, standard error = 0.010, P = 0.006), but not among participants in the ≥ 60-year-old group (β = -0.010, standard error = 0.011, P = 0.38). The findings suggest that taking preemptive actions of increasing physical activity may prevent the incidence of atherosclerosis.

Sex-based differences in the association of leisure-time physical activity with the risk of depression: the Ansan and Ansung study of the Korean Genome and Epidemiology Study (KoGES).

Depression is a serious mental disorder which is the leading cause of suicide. This study investigated the association between incident depression and 4-year leisure-time physical activity (PA) levels and/or resistance training (RT). This community-based Korean cohort included 3,967 participants without depression at baseline. The average PA-time (the total duration of moderate-intensity leisure-time PA) up to 4 years prior to baseline enrollment was calculated to evaluate the cumulative levels of PA. Participants were divided into four groups based on their average PA-time: "Non-PA," " <150 min/week," "150-299 min/week," and "≥300 min/week." Furthermore, based on compliance to PA guidelines (≥150 min/week of PA-time) and participation in RT, the participants were categorized into four subgroups: "Low-PA," "Low-PA+RT," "High-PA," and "High-PA+RT." A multivariate Cox proportional hazards regression model was used to assess the 4-year incidence of depression according to leisure-time PA levels and/or regularity of RT. During the mean 3.72 ± 0.69 years of follow-up, 432 participants (10.89%) developed depression. In women, performing 150-299 min/week of moderate-intensity leisure-time PA was associated with a 38% risk reduction for incident depression (HR, 0.62; CI, 0.43-0.89; p < 0.05), whereas more than 300 min/week of that was related to a 44% risk reduction for incident depression (HR, 0.56; CI, 0.35-0.89; p < 0.05) as compared to that in the Non-PA group. However, in men, there was no significant relationship between the amount of leisure-time PA per week and the risk of incident depression. Moreover, in both sexes, RT had no significant effect on depression in either the Low-PA or High-PA group. There was an inverse dose-response association between leisure-time PA levels and incident depression only in women, whereas adding RT to high levels of PA had no significant effect on depression in either sex.

#3293 ESTRADIOL REPLACEMENT MITIGATED BLOOD PRESSURE ELEVATION VIA SUPPRESSION OF NCC IN ANGIOTENSIN II-INFUSED OVARIECTOMIZED FEMALE RATS

Abstract Background and Aims Female rats excrete more urine sodium than male rats with similar blood pressure (BP). However, it is not clear whether the sex difference in pressure natriuresis is conserved in menopausal rats. We assessed whether the natriuretic response and renal sodium transporter activity in ovariectomized female rats infused with angiotensin II (ANGII) could be affected by estrogen supplementation. Method Six-week-old female Sprague-Dawley rats (n=30) were ovariectomized (OVX, n =20) or sham-operated (n=10) (−4 weeks, −4W). After 2 weeks, subcutaneous estradiol was administered to half of the OVX rats (n=10) for 4 weeks (-2W∼2W). ANGII was infused via the osmotic minipump in 60% of the rats for 2 weeks (0W∼2W). Six groups (female saline: FS, female ANGII: FA, OVX saline: OS, OVX ANGII: OA, OVX estradiol saline: OES, OVX estradiol ANGII: OEA) were sacrificed after 2 weeks of the ANGII infusion (2W). We also analyzed human data from the Korean Genome and Epidemiology Study (KoGES). Results ANGII-induced BP elevation was highest in the OA group, followed by the FA and OEA groups. Urine sodium tended to increase after ANGII infusion in FA and OEA but decreased in OA. Western blot results showed that cortical phosphorylated sodium chloride cotransporter (pNCC) tended to be augmented by ANGII treatment in FA and OA, but mitigated in OEA. Cortical ANGII type 2 receptor (AT2R) expression was significantly higher in estradiol-treated OVX rats than in OVX rats, irrespective of ANGII infusion. Similarly, the enhanced pNCC in ANGII-treated distal convoluted tubular cells was reversed by estradiol treatment. In KoGES data, urine sodium was significantly lower in postmenopausal women than in premenopausal women, despite the higher BP. Conclusion Estradiol reversed BP elevation and augmented the natriuretic response in ANGII-infused OVX rats and distal tubular cells via suppression of pNCC and increase of AT2R.

Inverse Association between Oxidative Balance Score and Incident Type 2 Diabetes Mellitus.

Mitigating the risk of type 2 diabetes mellitus (T2DM) can be achieved through the maintenance of a healthy weight, the adoption of a healthy diet, and engaging in regular physical activity. The oxidative balance score (OBS), an integrated measure of pro- and antioxidant exposure conditions, represents an individual's overall oxidative balance status. This study aimed to evaluate the association between OBS and T2DM incidence using data from a large, community-based, prospective cohort study. Data from 7369 participants aged 40-69 years who engaged in the Korean Genome and Epidemiology Study (KoGES) were analyzed. The hazard ratio (HR) and 95% confidence interval (CI) for T2DM incidence of sex-specific OBS tertile groups were calculated using univariable and multivariable Cox proportional hazard regression analyses. During the mean 13.6-year follow-up period, 908 men and 880 women developed T2DM. The fully-adjusted HR (95% CI) for incident T2DM of the middle and highest tertile groups, compared with the referent lowest tertile group, were 0.86 (0.77-1.02) and 0.83 (0.70-0.99) in men and were 0.94 (0.80-1.11) and 0.78 (0.65-0.94) in women, respectively. Individuals with a high OBS are at lower risk for the development of T2DM. This implies that lifestyle modification with more antioxidant properties could be a preventive strategy for T2DM.

Genetic association study identifies genetic variants for non-alcoholic fatty liver without comorbidities in the Korean population.

Non-alcoholic fatty liver (NAFL) refers to a disease in which fat builds up in the liver, similar to what occurs for those who drink a lot of alcohol, even in cases of not drinking alcohol at all or only in a small amount. Along with non-alcoholic steatohepatitis (NASH), NAFL is a type of non-alcoholic fatty liver disease (NAFLD). Currently, the prevalence of NAFLD is increasing worldwide. A wide range of comorbidities that can increase the risk of NAFLD includes obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. This study aimed to discover genetic variants for NAFL in the Korean population. Differing from previous studies, we conducted a genome-wide association study for NAFL in the selected subjects without comorbidities to rule out bias due to the inclusion of confounding effects of comorbidities. We grouped 424 NAFL cases and 5,402 controls from the Korean Genome and Epidemiology Study (KoGES) subjects without comorbidities such as dyslipidemia, type 2 diabetes, and metabolic syndrome. All subjects including cases and controls did not consume alcohol at all, or consumed less than 20g/day for men and less than 10g/day for women. The logistic association analysis adjusting for sex, age, BMI, and waist circumference identified one novel genome-wide significant variant (rs7996045, P = 2.3 × 10-8) for NAFL. This variant was located in the intron of CLDN10 and was not detected using previous conventional approaches in which confounding effects resulting from comorbidities were not considered in the study design stage. In addition, we detected several genetic variants showing suggestive association for NAFL (P < 10-5). The unique strategy in our association analysis of excluding major confounding factors provides, for the first time, an insight into the genuine genetic basis influencing NAFL.

Effect of the Interaction between Seaweed Intake and LPL Polymorphisms on Metabolic Syndrome in Middle-Aged Korean Adults

This study aimed to examine the effect of the interaction between seaweed (laver, kelp, and sea mustard) intake and lipoprotein lipase gene (LPL) rs17482735 genotypes on the incidence of metabolic syndrome (MetS). The Korean Genome and Epidemiology Study (KoGES) data of Korean adults aged 40–69 years were used in this study. Information on seaweed intake was obtained from the food frequency questionnaire. To investigate the interaction between seaweed intake and LPL rs17482735 genotypes on the incidence of MetS, multivariable Cox proportional hazard models were used after adjusting for confounding variables. There was no significant association in women, but men with TG and TT genotypes of rs17482753 had lower incidence of MetS (HR 0.83, 95% CI 0.71–0.95, p-value = 0.01), low HDL-cholesterol levels (HR 0.81, 95% CI 0.69–0.95, p-value = 0.01), high triglyceride levels (HR 0.83, 95% CI 0.70–0.99, p-value = 0.0471), and high blood pressure (HR 0.79, 95% CI 0.67–0.93, p-value = 0.004). Furthermore, the incidence of MetS was lower in men with the highest laver and total seaweed intake and TG and TT genotypes of rs17482735 (HR 0.60, 95% CI 0.43–0.84; HR 0.57, 95% CI 0.41–0.79, respectively). High seaweed intake was negatively associated with MetS, suggesting that LPL genetic variations, particularly in men, may be helpful in preventing MetS. These results demonstrate that seaweed intake considering LPL genotypes may be beneficial for preventing and treating MetS.

Characteristics of Hearing Loss Among Older Adults in the Korean Genome and Epidemiology Study: A Community-Based Longitudinal Cohort Study With an 8-Year Follow-up

This study investigated the 8-year incidence and progression of hearing loss (HL) and its types and examined the risk factors for changes in HL. This longitudinal cohort study analyzed data from the Korean Genome and Epidemiology Study (KoGES), an ongoing, prospective, community-based cohort study that has been conducted since 2001. Altogether, 1,890 residents of urban areas in Korea aged 45-75 years at time 1 (baseline) were included in the study. Pure-tone audiometry (PTA) testing was performed twice, at time 1 (2008-2009) and time 2 (2015-2018, follow-up), 8 years apart. HL grades were defined as seven mutually exclusive categories following the revised World Health Organization classification. Incidence was defined as PTA >20 dB HL in the better ear at time 2 among those without HL at time 1. Progression was defined as the progressive deterioration of HL among those with HL at time 1. The three types of HL constituted sensorineural (SNHL), conductive, and mixed HL. At time 1, 36.40% of patients were diagnosed with HL, which increased to 51.64% at time 2. The 8-year incidence of HL was 27.20%, and progressive deterioration of HL occurred in 23.11% of those with HL. SNHL was the most common type of HL, and its prevalence markedly increased at time 2. Multivariate analysis demonstrated that the incidence of HL was significantly associated with increasing age, male sex (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.07-2.81), and diabetes mellitus (OR, 1.43; 95% CI, 1.04-1.96). Alcohol consumption was a risk factor for HL deterioration among those with HL at time 1. The prevalence and deterioration of HL were extremely high among older adults, and age was the strongest risk factor for these changes. Therefore, timely screening and intervention are necessary to prevent HL and delay its deterioration among older adults.

Effects of gene-lifestyle environment interactions on type 2 diabetes mellitus development: an analysis using the Korean Genome and Epidemiology Study data

Purpose: This study focused on identifying the interaction effects of genetic and lifestyle-environmental factors on the development of type 2 diabetes mellitus (T2D). Methods: Study subjects were selected from the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2014. Data on genetic variations, anthropometric measurements, biochemical data, and seven lifestyle factors (diet, physical activity, alcohol drinking, smoking, sleep, depression, and stress) were obtained from 4,836 Koreans aged between 40 and 59 years, including those with T2D at baseline (n = 1,209), newly developed T2D (n= 1,298) and verified controls (n = 3,538). The genetic risk score (GRS) was calculated by using 11 single-nucleotide polymorphisms (SNPs) related to T2D development and the second quartile was used as the reference category. A Cox proportional hazards regression model was used to evaluate the associations of GRS and lifestyle factors with T2D risk, controlling for covariates.Results: Multivariate regression analysis revealed that GRS was the strongest risk factor for T2D, and body mass index (BMI), smoking, drinking, and spicy food preference also increased the risk. Lifestyle/environmental factors that showed significant interactions with GRS were BMI, current smoking, current drinking, fatty food preference, and spicy food preference. Conclusions: Interactions between genetic factors and lifestyle/environmental factors were associated with an increased risk of T2D. The results will be useful to provide a new perspective on genetic profiling for the earlier detection of T2D risk and clues for personalized interventions, which might be more effective prevention strategies or therapies in individuals with a genetic predisposition to T2D.

Obstructive sleep apnoea and long-term risk of incident diabetes in the middle-aged and older general population.

Obstructive sleep apnoea (OSA) is associated with increased risk of type 2 diabetes. However, results from large population-based prospective cohort studies are rare. The main aim of the present study was to investigate the relative risk of 8-year incident type 2 diabetes in relation to OSA severity in a prospective cohort study of middle-aged and older adults. A total of 2918 participants (mean age 59 years) of the Korean Genome and Epidemiology Study (KoGES), who underwent home-based overnight polysomnography at baseline examination between 2011 and 2014, were followed up 4-yearly between 2015-2018 and 2019-2021. A total of 1697 participants were present in both follow-ups. After excluding participants who had diabetes at baseline (n=481), a total of 1216 participants were eligible for the analyses. OSA at baseline was categorised by apnoea-hypopnoea index levels as non-OSA (0-4.9 events·h-1), mild OSA (5.0-14.9 events·h-1) and moderate-severe OSA (≥15.0 events·h-1). Incident type 2 diabetes was identified at each follow-up. Compared with non-OSA, participants with moderate-severe OSA had 1.5 times higher risk of developing type 2 diabetes at the end of the 8-year follow-up after adjusting for potential covariates (relative risk 1.50, 95% CI 1.02-2.21). In the same analytical models for 4-year relative risk of incident type 2 diabetes, none of the OSA groups were at significantly higher risk compared with the non-OSA group. Moderate-severe OSA, a modifiable risk factor, poses a higher risk of incident type 2 diabetes compared with non-OSA over an 8-year period in general middle-aged and older adults.