Korean Genome Research Articles

Genome assembly of the Korean intertidal mud-creeper Batillaria attramentaria

Batillaridae is a common gastropod family that occurs abundantly in the shallow coastal zone of the intertidal mudflats of the northwest Pacific Ocean, Australasia, and North America. In this family, Batillaria attramentaria is known for its biological invasion and colonization in estuarine and intertidal zones. It can endure and adapt the harsh intertidal conditions such as frequent temperature alteration, salinity, and air exposure. Therefore, we sequenced and assembled this Korean batillariid genome to get insight into its intertidal adaptive features. Approximately 53 Gb of DNA sequences were generated, and 863 scaffolds were assembled into a draft genome of 0.715 Gb with 97.1% BUSCO completeness value. A total of 40,596 genes were predicted. We estimated that B. attramentaria and Conus consors diverged about 230 million years ago (MYA) based on the phylogenetic analysis of closely related gastropod species. This genome study sets the footstep for genomics studies among native and introduced Batillaria populations and the Batillaridae family members.

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.

Association of non-high-density lipoprotein cholesterol trajectories with the development of non-alcoholic fatty liver disease: an epidemiological and genome-wide association study

BackgroundNon-alcoholic fatty liver disease (NAFLD) shares common risk factors with cardiovascular diseases. Effects of longitudinal trends in non-high-density lipoprotein (non-HDL) cholesterol on NAFLD development are not understood. This study aimed to assess the relationship between non-HDL cholesterol trajectories and the incidence of NAFLD and to identify genetic differences contributing to NAFLD development between non-HDL cholesterol trajectory groups.MethodsWe analyzed data from 2203 adults (aged 40–69 years) who participated in the Korean Genome and Epidemiology Study. During the 6-year exposure periods, participants were classified into an increasing non-HDL cholesterol trajectory group (n = 934) or a stable group (n = 1269). NAFLD was defined using a NAFLD-liver fat score > -0.640. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and the 95% confidence interval (CI) for the incidence of NAFLD in the increasing group compared with the stable group.ResultsA genome-wide association study identified significant single-nucleotide polymorphisms (SNPs) associated with NAFLD. During the median 7.8-year of event accrual period, 666 (30.2%) newly developed NAFLD cases were collected. Compared with the stable non-HDL group, the adjusted HR (95% CI) for the incidence of NAFLD in the increasing non-HDL cholesterol group was 1.46 (1.25–1.71). Although there were no significant SNPs, the polygenic risk score was highest in the increasing group, followed by the stable and control groups.ConclusionOur study indicates that lifestyle or environmental factors have a greater effect size than genetic factors in NAFLD progression risk. Lifestyle modification could be an effective prevention strategy for NAFLD for people with elevated non-HDL cholesterol.

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.

Assessment of Metabolic Syndrome Risk Based on Body Size Phenotype in Korean Adults: Analysis of Community-based Cohort Data

Purpose: Body size phenotypes can be regarded as an indicator of cardiovascular incidence risk factors. The aim of this study was to investigate the incidence of metabolic syndrome among metabolically healthy adults according to body size phenotype using Korean Genome &amp; Epidemiology Study [KoGES]-community based cohort from 2001-2002 to 2014.Methods: A prospective population-based cohort including 5,068 adults aged 40-69 years free from metabolic syndrome was included and divided into three phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), and metabolically healthy obesity (MHO). The time dependent Cox’s proportional hazards regression model was used to estimate the incidence of the metabolic syndrome after a follow-up 14 years.Results: In the demographic, health related variables-adjusted model (Model 3), the hazard ratio of the metabolic syndrome was 1.92 (CI 1.54-2.40) for MHOW, 2.88 (CI 2.32-3.58) for MHO among males, 1.89 (CI 1.51-2.37) for MHOW, 2.34 (CI 1.88-2.90) for MHO for females compared to MHNW, respectively.Conclusion: In conclusion, MHOW and MHO in both males and females increased the risk of metabolic syndrome compared to MHNW. Obesity management should be considered even in the absence of metabolic syndrome. Programs and resources should be provided for prevention of cardiovascular diseases and better quality of life.

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.

Gender Differences in the Risk for Incident Non-Alcoholic Fatty Liver Disease According to the Transition of Abdominal Obesity Status: A 16-Year Cohort Study.

Waist circumference (WC) is an important predictor of long-term adverse outcomes. We aimed at assessing the correlation between abdominal obesity (AO) patterns and non-alcoholic fatty liver disease (NAFLD). Data from 4467 adults aged 40-69 years and without NAFLD who participated in the Korean Genome and Epidemiology Study were analyzed. Participants were classified according to two-year WC pattern into four groups: persistent lean WC, improved AO, progressed to AO, and persistent AO. NAFLD was defined as NAFLD-liver fat score >-0.640. Multiple Cox proportional hazards regression analysis revealed that the fully adjusted hazard ratio (HR) (95% confidence intervals (CIs)) for NAFLD in persistent AO, progressed to AO, and improved AO groups compared to the persistent lean WC group was 1.33 (1.13-1.57), 1.73 (1.48-2.02), and 1.06 (0.84-1.33), respectively. Women in persistent AO or progressed to AO groups had significantly higher risk for NAFLD than those in persistent lean WC or improved AO groups. Men who had progressed to an AO event over two years had significantly higher risk for NAFLD than those without any AO event over two years. Maintaining lean WC and improving AO would be successful strategies for preventing NAFLD in women, while maintaining lean WC would be more effective in men.

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.

1263-P: Gender Differences in the Impact of Low Muscle Mass on Type 2 Diabetes Incidence—Eighteen-Year Follow-up Data from the Prospective Korean Genome and Epidemiology Study

Background: Current evidence suggests that diminished muscle mass is associated with an increased risk of diabetes. This study aimed to investigate whether the effect of low muscle mass (LMM) on incident diabetes varied depending on the tracking period using a prospective, longitudinal design. Methods: We recruited 6968 subjects without diabetes, aged 40 to 69 years, from the Korean Genomes and Epidemiology study and followed them to monitor the development of type 2 diabetes mellitus (T2DM). A standard 75-g oral glucose tolerance test was conducted at every 2-year follow-up visit. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and a weight-adjusted skeletal muscle mass was defined as muscle mass index (MMI). We assessed the relationship between LMM, the sex-specific lowest tertile of MMI, and the risk of developing T2DM using Cox regression models. Results: Of 6968 (47.4% men), 1846 progressed diabetes during the 18-year follow-up. LMM was associated with an increased risk of T2DM at 10 years and 10-18 years of follow-up in both genders after adjustment for confoundings. After additional adjustment for waist circumference, men with LMM were at significant risk of incident diabetes during the 10-year follow-up (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.28-1.86) but lost significance in 10-18 years., whereas women with LMM were at significantly increased risk (HR 1.32, 95% CI 1.03-1.69) only in 10-18 years. Over 18 years, LMM in men was consistently associated with an increased risk of diabetes from the initial period (at 2-year follow-up), whereas LMM in women has been shown to increase risk in the late period (from 12-year follow-up). Conclusion: This study showed that LMM is an independent risk factor for T2DM with gender differences over time. LMM was a constant risk factor for diabetes in men, whereas it affected the later onset of diabetes in women. Disclosure E.Kim: None. Y.Cho: None. O.Hong: None. S.Moon: None. J.Han: None. S.Yoo: None. N.H.Cho: None.

Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population.

We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns. The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed. In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10-83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10-6 (0.05/13,114); DEFB108B had the lowest p=5.94×10-15, followed by FAM86C1 (p=1.74×10-14), PSCA (p=1.81×10-14), and KLHDC4 (p=5.00×10-10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway. While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

740-P: Six Subclasses with Glucose and Insulin Curves during OGTTs Capture Distinct Metabolic Characteristics and the Most Common Pathway to T2D in a Cohort of Koreans

Heterogeneity of glucose abnormalities makes prevention and treatment of diabetes challenging. Subclasses of people at high risk have been identified based on glucose profiles during OGTTs. However, previous work on subclasses lacks longitudinal confirmation. Here, we used glucose and insulin during OGTTs and k-means clustering to classify subclasses of people without diabetes and then determined the model-derived beta-cell function (BCF) and insulin sensitivity (IS) within each subclass. We identified metabolic risk and the most common pathway to T2D by tracking transitions of subclasses over the 16-year Korean Genome Epi. Study. Participants underwent OGTTs every 2 years for up to 16 years or until diabetes (N=2682, BMI=24.4±2.9 kg/m2, age 49.8±7.6 y). 1) 6 subclasses: Cluster A: Normal BCF, Normal IS, B: Mildly impaired BCF and IS, C: Impaired BCF, mildly impaired IS, D: Strong BCF, impaired IS, E: Mildly impaired BCF, impaired IS, F: Strong BCF, severely impaired IS; 2) Cluster C had the highest risk for T2D, HR: 10.7 (8.0, 14.1), compared to cluster A, followed by Clusters E, B, F, and D; Transition from A to B and C was the most common pathway; A, B, and C together comprised 86% of the cohort. Clustering using glucose and insulin classified 6 subgroups showing distinct metabolic parameters and identified the most common pathway to T2D in Koreans. Disclosure J.Kim: None. H.Kang: None. S.T.Chung: None. A.Sherman: None. S.Kim: None. J.Ha: None. W.Yi: None. D.Kim: None. M.Im: None. S.Ryang: None. M.Kim: None. Y.Kim: None. I.Kim: None. Y.Kim: None. Funding Busan Economic Promotion Agency; National Research Foundation of Korea (2022H1D3A2A01063552); Korea Health Industry Development Institute (HI18C2383); dkNET New Investigator Pilot Program in Bioinformatics; National Institute of Diabetes and Digestive and Kidney Diseases

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.

Oxidative balance score is inversely associated with the incidence of non-alcoholic fatty liver disease

The contribution of the balance between overall oxidative stress and antioxidant status in non-alcoholic fatty liver disease (NAFLD) is unclear. The oxidative balance score (OBS) comprises dietary and lifestyle pro- and antioxidant components that indicate the overall oxidative stress burden. We investigated the association between OBS and the incidence of NAFLD in middle-aged and older Korean adults. Among the 10,030 participants of the Korean Genome and Epidemiology Study_Ansan and Ansung cohort, 5065 without NAFLD at baseline were selected for secondary analysis. OBS was categorized into quartiles. Multiple Cox proportional hazard regression analyses were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for NAFLD incidence by sex-specific OBS quartile groups after adjusting for confounders. During the follow-up period (median 13.4 years), 913 (43.2%) men and 1288 (43.9%) women were newly diagnosed with NAFLD. Compared with that of the lowest quartile (Q1) group, the adjusted HR (95% CI) for NAFLD incidence in Q2, Q3, and Q4 groups was 0.85 (0.71-1.00), 0.65 (0.54-0.78), and 0.50 (0.40-0.62) in men, and 0.85 (0.73-0.99), 0.66 (0.56-0.77), and 0.48 (0.40-0.59) in women, respectively, and for NAFLD incidence, per incremental change in OBS, was 0.90 (0.87-0.92) in men and 0.88 (0.86-0.90) in women. A higher OBS was significantly associated with a lower risk for NAFLD incidence. Maintaining a healthy lifestyle and an antioxidant-rich diet is a potentially viable strategy for preventing NAFLD.

#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.

CHANGES IN HEALTH BEHAVIORS FOLLOWING A HYPERTENSION DIAGNOSIS: THE KOREAN GENOME AND EPIDEMIOLOGY STUDY (2003-2018)

Objective: The management of hypertension requires a healthy lifestyle. However, it is unclear if individuals change their health behaviors after being diagnosed with hypertension. Thus, we aimed to evaluate the changes in smoking, alcohol consumption, exercise, and obesity following hypertension diagnosis using data from a community-based cohort. Design and method: We analyzed 5091 participants without hypertension at baseline from the Korean Genome and Epidemiology Study between 2003 and 2018. Participants were classified into the hypertension diagnosis group if they were diagnosed with hypertension by a physician during follow-up. Biennial health check-ups were used to measure health behaviors including smoking, drinking, exercise, and obesity. Generalized estimating equations were used to assess the differences by group and time and group-by-time interactions. Results: The group diagnosed with hypertension was more obese than the group not diagnosed with hypertension (p &lt; 0.001). However, smoking (p &lt; 0.001) and alcohol consumption (p &lt; 0.001) decreased over time in all participants, and exercise (p &lt; 0.001) increased. A group-by-time interaction was observed for smoking, with the group diagnosed with hypertension exhibiting greater reductions in smoking over time (p = 0.005). There were no significant interactions found for other behaviors. Conclusions: Our study provides limited evidence that a hypertension diagnosis alone may not be enough to encourage behavior change, except for smoking reduction. Thus, strategies to motivate behavior change need to be identified, given the importance of a healthy lifestyle in hypertension management.

Cardiocerebrovascular Disease or Fatty Liver Incidence Associated with Pattern of Metabolic Risk Factors and Nutritional Status of Korean Adults: A Prospective Cohort Study

Objectives: To determine the nutrient intake according to patterns of metabolic risk factors, and examine the relationship between patterns of metabolic risk factors and incidence of cardiocerebrovascular disease or fatty liver in Korean adults.Methods: Data from the Korean Genome and Epidemiology Study were used to analyze 7,019 adults aged 50-64 years old. Depending on patterns of metabolic risk factors, participants were classified into four categories: ‘normal, NOR’, ‘obesity risk factors, ORF’ , ‘vascular risk factors, VRF’, ‘cluster risk factors, CRF’. Cox regression analysis was used to evaluate the incidence of cardiocerebrovascular disease or fatty liver.Results: The mean adequacy ratio (MAR) of VRF pattern women was significantly lower than that of the normal women. In Model 3, the incidence of cardiovascular disease or fatty liver decreased by 64.4% (hazard ratio (HR), 0.36; 95% confidence interval (CI), 0.15-0.84) in MAR Q3 women compared to MAR Q1 women. In Model 2 adjusted for age and energy intake, the incidence of cardiovascular disease or fatty liver increased by 87.6% (HR, 1.88; 95% CI, 1.01-3.48) in CRF pattern women compared to NOR women, but there was no significant difference in Model 3.Conclusions: The study showed that among women, VRF patterns were associated with poor nutrient intake. There was an association between nutrient intake levels and metabolic risk factor patterns in women. Therefore, these findings can be used a basis to emphasize the need to establish nutrition management strategies tailored to individual’s metabolic risk status, for the prevention and management of metabolic syndrome complications.

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.

Prospective Associations between Dietary Patterns and Abdominal Obesity in Middle-Aged and Older Korean Adults.

This study aimed to identify major dietary patterns associated with abdominal obesity in middle-aged and older Korean adults. Data from the Korean Genome and Epidemiology Study were used. A total of 48,037 Korean adults aged ≥40 years without abdominal obesity at baseline were followed-up. Dietary assessment was conducted using a validated 106-item food-frequency questionnaire, and dietary patterns were identified using factor analysis. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥85 cm for women, according to the Korean Society for the Study of Obesity. Multivariable Cox proportional-hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the future risk of abdominal obesity for each dietary pattern after adjusting for potential covariates. After an average follow-up of 4.89 years, we reported 5878 cases (1932 men and 3946 women) of abdominal obesity. Based on factor analysis, three major dietary patterns were identified in both men and women: the "healthy", "coffee and sweets", and "multi-grain" patterns. In the fully adjusted model, the "healthy" pattern was inversely associated with the incidence of abdominal obesity (HR for fourth vs. first quartile: 0.86; 95% CI: 0.75-0.98; p for trend = 0.0358 for men; HR for fourth vs. first quartile: 0.90; 95% CI: 0.83-0.99; p for trend = 0.0188 for women), whereas the "coffee and sweets" pattern was positively associated with it (HR for fourth vs. first quartile: 1.23; 95% CI: 1.08-1.40; p for trend = 0.0495 for men; HR for fourth vs. first quartile: 1.14; 95% CI: 1.04-1.25; p for trend = 0.0096 for women). In contrast, the "multi-grain" pattern in men and women showed no significant association with the incidence of abdominal obesity. Diets rich in colorful vegetables, seaweeds, mushrooms, tubers, fruits, soy products, and fish and low in coffee, sweets, and oils/fats might be favorable for reducing the future risk of abdominal obesity, particularly in middle-aged and older Korean adults.

Association of NAFLD with FGF21 Polygenic Hazard Score, and Its Interaction with Protein Intake Level in Korean Adults.

Fibroblast growth factor 21 (FGF21) is a hormone that participates in the regulation of energy homeostasis and is induced by dietary protein restriction. Preclinical studies have suggested that FGF21 induction exerts a protective effect against non-alcoholic fatty liver disease (NAFLD), while human studies have revealed elevated levels of and potential resistance to FGF21 in patients with NAFLD. However, whether the FGF21 pathway also contributes to NAFLD risk at the genetic level remains uncertain. A few attempts to investigate the impact of individual genetic variants at the loci encoding FGF21 and its receptors on NAFLD risk have failed to establish a clear association due to a limited effect size. Therefore, this study aimed to (1) develop a polygenic hazard score (PHS) for FGF21-related loci that are associated with NAFLD risk and (2) investigate the effect of its interaction with protein intake level on NAFLD risk. Data on 3501 participants of the Korean Genome Epidemiology Study (Ansan-Ansung) were analyzed. Eight single-nucleotide polymorphisms of fibroblast growth factor receptors and beta-klotho were selected for PHS determination using forward stepwise analysis. The association between the PHS and NAFLD was validated (p-trend: 0.0171 for men and <0.0001 for women). Moreover, the association was significantly modulated by the protein intake level in all participants as well as women (p-interaction = 0.0189 and 0.0131, respectively) but not in men. In particular, the women with the lowest PHS values and a protein intake lower than the recommended nutrient intake (RNI) exhibited a greater NAFLD risk (HR = 2.021, p-trend = 0.0016) than those with an intake equal to or greater than the RNI; however, those with higher PHS values had a high risk, regardless of protein intake level. These findings demonstrate the contribution of FGF21-related genetic variants and restricted protein intake to NAFLD incidence.