Korean Genome And Epidemiology Study Research Articles

#2961 Association of polygenic risk scores for blood pressure with incidence of hypertension and chronic kidney disease

Abstract Background and Aims Genetic risk for elevated blood pressure (BP) has been associated with a higher risk of hypertension and cardiovascular disease. However, the generalizability of previous findings has been limited due to a lack of studies among Asian populations. This study aimed to investigate whether genetic risk for BP predicts the incidence of hypertension and chronic kidney disease (CKD) in Asian populations. Method We performed genome-wide association studies for systolic and diastolic BP (SBP and DBP, respectively) using data from the Korean Genome and Epidemiology Study (KoGES). We then meta-analyzed these results with summary statistics from Biobank Japan to construct polygenic risk scores (PRSs) and examined the association between BP PRSs and incident hypertension or CKD. This study included participants without hypertension, cardiovascular disease, or CKD at baseline (n=4349, median age 48.5 years, 48.8% men). Participants were categorized into four groups based on their PRS percentile (<5, 5–50, 50–95, >95). Results As the PRS percentile increases, the median SBP and DBP at baseline also increase. Compared to the lowest SBP PRS percentile, higher PRS percentile was associated with increased risk of hypertension (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.22–1.83 for PRS percentile 5–50, HR 1.94, 95% CI 1.58–2.38 for PRS percentile 50–95, and HR 2.35, 95% CI 1.80–3.07 for PRS percentile >95). Elevated DBP PRS was also associated with higher risk of hypertension (HR 1.27, 95% CI 1.04–1.54 for PRS percentile 5–50, HR 1.72, 95% CI 1.41–2.09 for PRS percentile 50-95, and HR 2.09, 95% CI 1.60–2.72 for PRS percentile >95). The highest PRS percentile for SBP and DBP was associated with earlier onsets of hypertension by median 11 and 9 years, respectively, compared to the lowest PRS percentile for SBP and DBP. However, both SBP and DBP RPSs were not associated with incident CKD. Conclusion Genetic risk for elevated BP was associated with a higher risk of incident hypertension and earlier onset of hypertension in the Asian population. However, there was no association between PRS for elevated BP and the incidence of CKD.

Association between traditional Korean fermented vegetables (kimchi) intake and serum lipid profile: using the Korean Genome and Epidemiology Study (KoGES) cohort.

Dyslipidemia is a major health issue worldwide. There is growing interest in understanding the potential role of kimchi consumption on serum lipid profiles. However, there are limited epidemiological studies available on this topic. Therefore, this study aims to investigate the association between kimchi intake and serum lipid profiles. We conducted an epidemiological study on participants (aged 40-69 years old) selected from the Health Examinees (HEXA) cohort study (n = 61,761). Four types of kimchi, including Baechu kimchi (cabbage kimchi), Kkakdugi (radish kimchi), Nabak kimchi/Dongchimi (a type of water kimchi made with fermented vegetables), and other kimchi, were assessed by a 106-food item semi-quantitative validated food frequency questionnaire (FFQ). Each kimchi intake is the average value calculated from the FFQ of the baseline and follow-up surveys. Fasting blood data were obtained at baseline and follow-up visits. Linear regression was used to examine the relationship between the intake of kimchi and the change in serum lipid profiles. The mean years between the baseline survey and a follow-up survey was 4.97 years. In this study, compared to the lowest category (< 1 serving/day), Baechu kimchi intake (2- < 3 servings/day) had more negative correlations with the change in values of total cholesterol (β: -1.600, 95% confidence interval [CI, -2.744, -0.456]), triglycerides (β: -3.372, 95% CI [-5.414, -1.330]), and low-density lipoprotein cholesterol (β: -1.155, 95% CI [-2.214, -0.095]) in women. In men, Baechu kimchi intake (2- < 3 servings/day) had a more positive correlation associated with the changes in values of high-density lipoprotein cholesterol (β: 0.049, 95% CI [0.031, 0.907]) compared to the lowest intake category (< 1 serving/day). Among Korean adults, consumption of kimchi, particularly Baechu kimchi, was found to be associated with improvements in serum lipid profiles. Further studies are required to conduct additional interventions to confirm the association between kimchi and serum lipid profiles.

C-reactive protein to albumin ratio and risk of incident metabolic syndrome in community-dwelling adults: longitudinal findings over a 12-year follow-up period.

The C-reactive protein to albumin (CRP/Alb) ratio has emerged as a novel biomarker for various inflammatory diseases. This study aimed to evaluate the association between the CRP/Alb ratio and incident metabolic syndrome (MetS) with a large-sample, community-based Korean cohort over a 12-year follow-up period. Among 10,030 participants, a total of 6205 participants aged 40-69 years without MetS were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline CRP/Alb ratio was divided into quartiles. The definition of newly developed MetS was the one proposed by the 2009 Joint Interim Statement of Circulation. Hazard ratios (HRs) with 95% confidence intervals (CIs) for incident MetS were calculated using multivariable Cox proportional hazards regression models after adjusting for potentially confounding variables. During the 12-year follow-up period, MetS developed in 2535 subjects (40.9%, 2535/6205) with an incidence rate of 5.6-11.9 (over 2 years). Compared to the reference first quartiles, the HRs (95% CIs) of incident MetS in the second, third, and fourth quartiles increased in a dose-response manner. Compared to the reference quartile, the HRs (95% CIs) of the incidence of MetS for the second, third, and fourth quartiles of CRP/Alb ratio were 1.12 (0.99-1.27), 1.24 (1.11-1.40), and 1.51 (1.34-1.69) after adjusting for age, sex, smoking status, alcohol intake, physical activity, total cholesterol, mean arterial pressure, HOMA-IR, and total energy intake. High CRP/Alb ratio at baseline may be a useful surrogate indicator of future incident MetS.

Expansion of a food composition database for the food frequency questionnaire in the Korean Genome and Epidemiology Study (KoGES): a comprehensive database of dietary antioxidants and total antioxidant capacity.

This study constructed a comprehensive database of dietary antioxidants and total antioxidant capacity (TAC) to facilitate the estimation of daily antioxidant intake using a food frequency questionnaire (FFQ). This database was applied to 3 general population-based cohorts (n=195,961) within the Korean Genome and Epidemiology Study (KoGES). To establish a database of 412 foods derived from recipes of a 106-item FFQ, we followed a pre-established standardized protocol. This included the selection of source databases, matching of foods, substitution of unmatched items with identical foods and input of values, and assessment of coverage. For each food, the TAC was estimated by summing the individual antioxidant capacities, calculated by multiplying the amount of each antioxidant by its vitamin C equivalent antioxidant capacity. We identified 48 antioxidants across 5 classes: retinol, carotenoids, vitamins C and E, and flavonoids, with flavonoids divided into 7 subclasses. TAC values were then established. Coverage exceeded 90.0% for retinol, carotenoids, vitamin C, and vitamin E, while coverage for flavonoids was 60.9%. The daily intakes of 4 antioxidant classes-all but vitamin E-were higher in women than in men. The Ansan-Ansung cohort exhibited the highest levels of dietary TAC, vitamin E, and flavonoids, while the Health Examinees Study cohort displayed the highest values for retinol, carotenoids, and vitamin C. We customized a comprehensive antioxidant database for the KoGES FFQ, achieving relatively high coverage. This expansion could support research investigating the impact of dietary antioxidants on the development of chronic diseases targeted by the KoGES.

Exploring the role of apolipoprotein E gene promoter polymorphisms in susceptibility to normal-tension glaucoma in a Korean population

Glaucoma, particularly primary open-angle glaucoma (POAG), poses a significant global health concern. Distinguished by intraocular pressure (IOP), POAG encompasses high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Apolipoprotein E (APOE) is a multifaceted protein with roles in lipid metabolism, neurobiology, and neurodegenerative diseases. However, controversies persist regarding the impact of APOE single-nucleotide polymorphisms (SNPs) on open-angle glaucoma and NTG. This study aimed to identify APOE-specific SNPs influencing NTG risk. A cohort of 178 patients with NTG recruited from Uijeongbu St. Mary’s Hospital and 32,858 individuals from the Korean Genome and Epidemiology Study (KoGES) cohort were included in the analysis. Genotype and haplotype analyses were performed on three promoter SNPs (rs449647, rs769446, and rs405509) and two exonic SNPs (rs429358 and rs7412) located on chromosome 19. Among the five SNPs, rs769446 genotypes exhibited significant differences between cases and controls. The minor allele C of rs769446 emerged as a protective factor against NTG. Furthermore, haplotype analysis of the five SNPs revealed that the A-T-G-T-T haplotype was a statistically significant risk factor for NTG. This study indicated an association between APOE promoter SNPs and NTG in the Korean population. Further studies are required to understand how APOE promoter SNPs contribute to NTG pathogenesis.

Nutrition survey methods and food composition database update of the Korean Genome and Epidemiology Study.

This study presents the nutrition survey methods and the updated food composition database for the Korean Genome and Epidemiology Study (KoGES). The KoGES, which is the largest and longest cohort study in Korea, aims to identify genetic and environmental factors associated with chronic diseases. This study has collected dietary data using a validated semi-quantitative food frequency questionnaire and/or the 24-hour recall method. However, these dietary survey methods use different food composition databases, and their nutritional values are out of date. Therefore, it became necessary to update the food composition database by correcting errors in nutrient analysis values to reflect improvements in the performance of food ingredient analysis equipment, revising international values ​​to analysis values ​​of Korean agricultural products, adjusting nutrient units, and adding newly reported nutrients related to chronic diseases. For this purpose, we integrated the different food composition databases used in each nutrition survey, updated 23 nutrients, and expanded 48 new nutrients for 3,648 food items using the latest reliable food composition databases published by national and international institutions. This revised food composition database may help to clarify the relationship between various nutrients and chronic diseases. It could serve as a valuable resource for nutritional, epidemiological, and genomic research and provide a basis for determining public health policies.

Difference in association of carbohydrate intake with all-cause mortality between middle-aged and older Korean adults with and without diabetes mellitus: A prospective study

The relationship between diet and health, particularly the role of carbohydrates, has been extensively studied. However, carbohydrate intake based on individual health conditions remains unclear. Here, we aimed to investigate whether the association between carbohydrate intake and all-cause mortality varied between individuals with and without diabetes mellitus (DM). This prospective cohort study used data from the Korean Genome and Epidemiology Study (KoGES). Overall, 143,050 participants were included, with 10.1% having DM. Dietary intake was assessed using a semiquantitative food frequency questionnaire. Cox proportional hazards regression models were used to assess the association between carbohydrate intake and mortality after adjusting for confounders. The study showed that 5436 deaths occurred during the median follow-up period of 10.1 years. A significant interaction between carbohydrate intake and DM was observed in the study population (interaction p=0.061). Higher carbohydrate intake proportion was associated with an increased risk of all-cause mortality among individuals with DM (adjusted hazard ratio [HR], p-value=1.10 [1.01-1.20], p=0.032). Conversely, no association was observed between the proportion of carbohydrate intake and all-cause mortality in participants without DM. Additionally, both total sugar and added sugar intakes were associated with an increased risk of all-cause mortality in participants with DM (adjusted HR, p-value=1.02 [1.01-1.04], p<0.001 and 1.18 [1.13-1.24], p<0.001). High carbohydrate (%) and added sugar intake were associated with an increased mortality risk in individuals with DM. Reducing carbohydrate intake and opting for healthy carbohydrates to mitigate mortality risk may be beneficial for individuals with DM, particularly when compared with the general population.

The Fatty Liver Index's Association with Incident Chronic Kidney Disease in Korean Middle-Aged Adults: A Community-Based Cohort Study.

(1) Background: The relationship between nonalcoholic fatty liver disease (NAFLD) and incident chronic kidney disease (CKD) is unclear, and long-term follow-up data are limited. Therefore, this study aimed to evaluate whether NAFLD, as assessed by the fatty liver index (FLI), could predict the development of CKD in a community-based Korean cohort over 16 years. (2) Methods: Among the 10,030 total participants, 7778 patients without CKD were selected from the Korean Genome and Epidemiology Study (KoGES). The FLI grade ranged from 0 to 100 and was divided into three groups: low (FLI, <30), intermediate (FLI, 30-59), and high (FLI, ≥60). An estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or the development of proteinuria was considered to indicate incident CKD. (3) Results: During the 16-year follow-up period, 919 individuals (11.8%) developed CKD. The HRs of incident CKD in the intermediate FLI group (30-59) and high FLI group (≥60) increased compared with the reference low FLI group (<30) after adjusting for potentially confounding variables. NAFLD, as assessed by the FLI, was an independent risk factor for CKD. (4) Conclusions: Our findings suggest that the FLI, a simple surrogate biomarker of fatty liver disease, may be used to identify people at high risk of incident CKD in clinical practice.

Incorporating functional annotation with bilevel continuous shrinkage for polygenic risk prediction

BackgroundGenetic variants can contribute differently to trait heritability by their functional categories, and recent studies have shown that incorporating functional annotation can improve the predictive performance of polygenic risk scores (PRSs). In addition, when only a small proportion of variants are causal variants, PRS methods that employ a Bayesian framework with shrinkage can account for such sparsity. It is possible that the annotation group level effect is also sparse. However, the number of PRS methods that incorporate both annotation information and shrinkage on effect sizes is limited. We propose a PRS method, PRSbils, which utilizes the functional annotation information with a bilevel continuous shrinkage prior to accommodate the varying genetic architectures both on the variant-specific level and on the functional annotation level.ResultsWe conducted simulation studies and investigated the predictive performance in settings with different genetic architectures. Results indicated that when there was a relatively large variability of group-wise heritability contribution, the gain in prediction performance from the proposed method was on average 8.0% higher AUC compared to the benchmark method PRS-CS. The proposed method also yielded higher predictive performance compared to PRS-CS in settings with different overlapping patterns of annotation groups and obtained on average 6.4% higher AUC. We applied PRSbils to binary and quantitative traits in three real world data sources (the UK Biobank, the Michigan Genomics Initiative (MGI), and the Korean Genome and Epidemiology Study (KoGES)), and two sources of annotations: ANNOVAR, and pathway information from the Kyoto Encyclopedia of Genes and Genomes (KEGG), and demonstrated that the proposed method holds the potential for improving predictive performance by incorporating functional annotations.ConclusionsBy utilizing a bilevel shrinkage framework, PRSbils enables the incorporation of both overlapping and non-overlapping annotations into PRS construction to improve the performance of genetic risk prediction. The software is available at https://github.com/styvon/PRSbils.

Evaluation of penalized and machine learning methods for asthma disease prediction in the Korean Genome and Epidemiology Study (KoGES)

BackgroundGenome-wide association studies have successfully identified genetic variants associated with human disease. Various statistical approaches based on penalized and machine learning methods have recently been proposed for disease prediction. In this study, we evaluated the performance of several such methods for predicting asthma using the Korean Chip (KORV1.1) from the Korean Genome and Epidemiology Study (KoGES).ResultsFirst, single-nucleotide polymorphisms were selected via single-variant tests using logistic regression with the adjustment of several epidemiological factors. Next, we evaluated the following methods for disease prediction: ridge, least absolute shrinkage and selection operator, elastic net, smoothly clipped absolute deviation, support vector machine, random forest, boosting, bagging, naïve Bayes, and k-nearest neighbor. Finally, we compared their predictive performance based on the area under the curve of the receiver operating characteristic curves, precision, recall, F1-score, Cohen′s Kappa, balanced accuracy, error rate, Matthews correlation coefficient, and area under the precision-recall curve. Additionally, three oversampling algorithms are used to deal with imbalance problems.ConclusionsOur results show that penalized methods exhibit better predictive performance for asthma than that achieved via machine learning methods. On the other hand, in the oversampling study, randomforest and boosting methods overall showed better prediction performance than penalized methods.

Association between Processed Meat Protein Consumption and Incident Osteoporosis in Adults Aged 50 Years and Older: A Prospective Cohort Study Based on Korean Genome and Epidemiology Study Data (2005-2020).

Osteoporosis is one of the inevitable diseases affecting an aging society, substantially impacting the quality of life of its population. Protein intake has been shown to be beneficial in reducing the incidence of osteoporosis, and the effects of both animal and vegetable proteins have been studied. However, the relationship between processed meat consumption and osteoporosis has not been studied in Korea. Therefore, we aimed to analyze the correlation between processed meat consumption and incident osteoporosis in adults. Our analysis included 1,260 adults aged 50 years and older from the Korean Genome and Epidemiology Study (KoGES), recruited between 2005 and 2020. Participants were categorized into two groups according to their processed meat intake, assessed using a semi-quantitative 103-food item food frequency questionnaire. Diagnosis of osteoporosis was based on questionnaire answers. Multiple Cox hazard regression analyses were conducted to examine the association between processed meat intake and incident osteoporosis. During an average follow-up period of 8.8 years, 230 participants developed osteoporosis. According to the Cox proportional regression models, the hazard ratio (95% confidence interval) of incident osteoporosis in the high intake group was 0.62 (0.41-0.94), compared to the low intake group after adjusting for confounding variables. These findings reveal that processed meat protein intake is inversely related to the incidence of osteoporosis in adults aged 50 years and older. This in turn suggests that processed meat intake can be proposed as an additional strategy to prevent osteoporosis.

P1196 Genomic structural variation and polygenic risk score for Inflammatory Bowel Disease

Abstract Background Genome-wide association studies (GWAS) of patients with inflammatory bowel disease (IBD) have identified multiple single-nucleotide polymorphisms (SNPs) and genetic variants involving structural changes in the DNA sequence. SNPs and structural variants (SVs) can play a crucial role in IBD pathogenesis. In this study, we evaluated large deletions induced by SVs in patients with IBD. Additionally, we evaluated the ethnic contribution to a polygenic risk score (PRS) for IBD. Methods Seventy-five Patients with IBD of Korean ancestry from Seoul National University Bundang Hospital (SNUBH) were subjected to whole-genome sequencing (49 patients with UC and 26 patients with CD). SVs involving large deletions were detected and analyzed by using the Genome Aggregation Database (gnomAD) and AnnotSV. The SVs were prioritized based on a list of 241 IBD-associated SNPs identified in the previous GWAS. The prediction performance of European- and Korean-derived PRSs for IBD was also evaluated. For calculating PRS, we applied previously published models derived from the European and Korean populations, respectively, and used Korean Genome and Epidemiology Study (KoGES) database as the Korean controls. Results We found a total of 146 SVs involving large deletions in the IBD cohort. Among them, 10 SVs were annotated as likely pathogenic, according to AnnotSV and American College of Medical Genetics and Genomics guidelines; 24 SVs had the probability of being loss-of-function intolerant (pLI ≥ 0.9). We found that the frequency of large deletions that overlapped with the regions coding NOTCH1, HGF, PTPN2, and SENP7 were rare in the IBD cohort compared to the gnomAD population (Table). The large deletions that overlapped with the regions coding IL2RA, ITGA4, BANK1, and STAT3 were identified in the IBD cohort but not in the gnomAD population. The PRS for IBD in the IBD cohort was significantly higher than that in the Korean controls under the Korean- or European-derived model (Figure A). However, the PRSs for CD or UC were not able to distinguish patients with CD and UC in the IBD cohort (Figure B and C). Conclusion Our finding suggests that SVs involving large deletion may be an important genomic variability in predicting the development of IBD. The PRS for IBD can predict IBD development without ethnic specificity.

Higher adherence to a Mediterranean-type diet is associated with reduced psychosocial stress levels in baby boomers: a cross-sectional study.

This study investigated the relationship between adherence to the Mediterranean diet among Korean baby boomers and their levels of psychosocial stress. The study included 1,656 adults (889 men and 797 women) born between 1955 and 1963 who participated in the 2005-2006 survey of the community-based Korean Genome and Epidemiology Study (KoGES). The Mediterranean-type diet score (MTDS) was calculated from the semi-quantitative food frequency questionnaire (SQFFQ) data. The psychosocial stress levels were calculated using the psychosocial well-being index-short form (PWI-SF). Logistic regression analyses were performed to analyze the association between the MTDS (tertiles) and the prevalence of high psychosocial stress by gender. The ranges of the MTDS tertile groups were T1 (20-33 points), T2 (34-37 points), and T3 (38-39 points) for men, T1 (20-33 points), T2 (34-37 points), and T3 (38-48 points) for women. In both men and women, the consumption of whole grains, potatoes, fruits, vegetables, legumes, and fish increased with higher MTDS, while the consumption of red meat and dairy products decreased (P for trend < 0.05). As MTDS score increased the intake of energy, fiber, vitamins, and minerals (P for trend < 0.05). Men in the highest MTDS tertile had a 41% lower odds ratio (OR) of high psychosocial stress compared with those in the lowest tertile (OR, 0.59; 95% confidence interval [CI], 0.38-0.91). Similarly, women in the highest tertile of the MTDS had a 39% lower OR of high psychosocial stress compared with those in the lowest tertile (OR, 0.61; 95% CI, 0.40-0.95). Promoting adherence to the Mediterranean diet among baby boomers may have a positive impact on reducing their levels of psychosocial stress.

Longitudinal Relationships between Cigarette Smoking and Increases Risk for Incident Metabolic Syndrome: 16-year Follow-up of the Korean Genome and Epidemiology Study (KOGES)

Longitudinal Relationships between Cigarette Smoking and Increases Risk for Incident Metabolic Syndrome: 16-year Follow-up of the Korean Genome and Epidemiology Study (KOGES)

Dietary cholesterol intake is not associated with the development of chronic kidney disease: Results from two Korean cohort studies

Background and aimsAlthough dyslipidemia is a major risk factor for chronic kidney disease (CKD), the relationship between dietary cholesterol and CKD remains unknown. We investigated the association between cholesterol intake and CKD risk. Methods and resultsThe Korea National Health and Nutrition Examination Survey (KNHANES) 2019–2021 (n = 13,769) and the Korean Genome and Epidemiology Study (KoGES) (n = 9225) data were used for this study. Cholesterol intake was assessed using a 24-h recall food frequency questionnaire, and participants were categorized into three groups (T1, T2, and T3) based on cholesterol intake. Primary outcomes were prevalence and incidence of CKD. Higher cholesterol intake was modestly associated with increased serum levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol in the KNHANES. However, we found no significant association between cholesterol intake and CKD prevalence in the KNHANES, regardless of a history of hypercholesterolemia. In the KoGES, during a median follow-up of 11.4 years, cholesterol intake was not associated with incident CKD in participants without hypercholesterolemia (hazard ratio [HR] per 10 mg increase, 1.00; 95 % confidence interval [CI], 0.99–1.01) and in those with hypercholesterolemia (HR, 1.01; 95 % CI, 0.98–1.04). Egg consumption also showed no significant association with the risk of incident CKD. Additionally, cholesterol intake had no significant interaction on the relationships between serum cholesterol levels and incident CKD. ConclusionAlthough cholesterol intake was associated with increased serum cholesterol levels, it was not associated with CKD prevalence and incidence. Our findings suggest that reducing cholesterol intake alone may not be sufficient to prevent CKD.

Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study.

Diabetes is characterized by persistently high blood glucose levels and severe complications and affects millions of people worldwide. In this study, we explored the epigenetic landscape of diabetes using data from the Korean Genome and Epidemiology Study (KoGES), specifically the Ansung-Ansan (AS-AS) cohort. Using epigenome-wide association studies, we investigated DNA methylation patterns in patients with type 2 diabetes mellitus (T2DM) and those with normal glucose regulation. Differential methylation analysis revealed 106 differentially methylated probes (DMPs), with the 10 top DMPs prominently associated with TXNIP, PDK4, NBPF20, ARRDC4, UFM1, PFKFB2, C7orf50, and ABCG1, indicating significant changes in methylation. Correlation analysis highlighted the association between the leading DMPs (e.g., cg19693031 and cg26974062 for TXNIP and cg26823705 for NBPF20) and key glycemic markers (fasting plasma glucose and hemoglobin A1c), confirming their relevance in T2DM. Moreover, we identified 62 significantly differentially methylated regions (DMRs) spanning 61 genes. A DMR associated with PDE1C showed hypermethylation, whereas DMRs associated with DIP2C, FLJ90757, PRSS50, and TDRD9 showed hypomethylation. PDE1C and TDRD9 showed a strong positive correlation between the CpG sites included in each DMR, which have previously been implicated in T2DM-related processes. This study contributes to the understanding of epigenetic modifications in T2DM. These valuable insights can be utilized in identifying potential biomarkers and therapeutic targets for effective management and prevention of diabetes.

Association between experience of insulin resistance and long-term cardiovascular disease risk: findings from the Korean Genome and Epidemiology Study (KOGES).

Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults. We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders. Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07-1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01-1.84). Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.

THU245 Association Between Sleep Duration And Incident Diabetes Mellitus In Healthy Subjects: A 12-year Longitudinal Cohort Study

Abstract Disclosure: W. Kim: None. J. Huh: None. Objective: Previous studies demonstrated that inadequate sleep, including the deprivation of absolute sleep duration and poor sleep quality, was associated with a higher risk of type 2 diabetes mellitus (DM) and obesity. This study aimed to investigate whether sleep duration and/or quality is associated with incident DM. Methods: The study population consisted of participants in the ongoing Korean Genome and Epidemiology Study (KoGES)-Ansung and Ansan Cohort Study, a rural, community-based, prospective study. A total of 8,816 of 10,030 healthy participants were enrolled in a prospective cohort study. DM was diagnosed as fasting glucose ≥126 mg/dL or 2-h post-loading glucose ≥200 mg/dL. Sleep du-ration and quality questionnaires were completed. Sleep duration was classified into four groups: 6 &amp;lt;, 6-7, 8-9, 9 h/day. Sleep quality was assessed in participants with sleep duration of &amp;lt; 10 h/day using the Epworth Sleepiness Scale (ESS) which measures an excessive daytime sleepiness in individuals. Results: During the 14-year follow-up period, 18% (1630/8816) were diagnosed with DM. A U-shaped relationship was observed between sleep duration and incident DM, with the highest risk observed when sleep duration was 10 ≥ h/day (Hazard ratios (HR) 1.65 [1.25–2.17]). This group exhibited decreased insulin glycogenic index, a marker of insulin secretory function, during the study period. Among study participants who slept less than 10 h/day, the risk of incident DM increased when the ESS score was &amp;gt; 10. Conclusion: We found that the association between sleep duration and incident DM was U-shaped; both short (≤5 h) and long (≥10 h) sleep duration were associated with an increased risk for the occurrence of incident DM. When sleep duration was 10 h or longer per day, there was a tendency to develop DM due to decreased insulin secretory function. Even if the sleep duration is less than 10 h, the likelihood of developing diabetes is greater when the quality of sleep decreases. Presentation: Thursday, June 15, 2023

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.