Korean Genome Epidemiology Study Research Articles

Machine Learning-Based Identification of Diagnostic Biomarkers for Korean Male Sarcopenia Through Integrative DNA Methylation and Methylation Risk Score: From the Korean Genomic Epidemiology Study (KoGES).

Sarcopenia, characterized by a progressive decline in muscle mass, strength, and function, is primarily attributable to aging. DNA methylation, influenced by both genetic predispositions and environmental exposures, plays a significant role in sarcopenia occurrence. This study employed machine learning (ML) methods to identify differentially methylated probes (DMPs) capable of diagnosing sarcopenia in middle-aged individuals. We also investigated the relationship between muscle strength, muscle mass, age, and sarcopenia risk as reflected in methylation profiles. Data from 509 male participants in the urban cohort of the Korean Genome Epidemiology Study_Health Examinee study were categorized into quartile groups based on the sarcopenia criteria for appendicular skeletal muscle index (ASMI) and handgrip strength (HG). To identify diagnostic biomarkers for sarcopenia, we used recursive feature elimination with cross validation (RFECV), to pinpoint DMPs significantly associated with sarcopenia. An ensemble model, leveraging majority voting, was utilized for evaluation. Furthermore, a methylation risk score (MRS) was calculated, and its correlation with muscle strength, function, and age was assessed using likelihood ratio analysis and multinomial logistic regression. Participants were classified into two groups based on quartile thresholds: sarcopenia (n = 37) with ASMI and HG in the lowest quartile, and normal ranges (n = 48) in the highest. In total, 238 DMPs were identified and eight probes were selected using RFECV. These DMPs were used to build an ensemble model with robust diagnostic capabilities for sarcopenia, as evidenced by an area under the receiver operating characteristic curve of 0.94. Based on eight probes, the MRS was calculated and then validated by analyzing age, HG, and ASMI among the control group (n = 424). Age was positively correlated with high MRS (coefficient, 1.2494; odds ratio [OR], 3.4882), whereas ASMI and HG were negatively correlated with high MRS (ASMI coefficient, -0.4275; OR, 0.6521; HG coefficient, -0.3116; OR, 0.7323). Overall, this study identified key epigenetic markers of sarcopenia in Korean males and developed a ML model with high diagnostic accuracy for sarcopenia. The MRS also revealed significant correlations between these markers and age, HG, and ASMI. These findings suggest that both diagnostic models and the MRS can play an important role in managing sarcopenia in middle-aged populations.

Sex differences in the relationship between serum total bilirubin and risk of incident metabolic syndrome in community-dwelling adults: Propensity score analysis using longitudinal cohort data over 16 years

BackgroundResearch on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study.MethodsData were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40–69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline.ResultsWith increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80–1.24) for men and 0.80 (0.65–0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285).ConclusionSerum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.

노인성 류마티스 관절염에서의 당뇨병 위험: 한국인유전체역학조사사업(KoGES) 자료를 이용하여

Rheumatoid arthritis (RA) is one of representative geriatric diseases caused by a combination of various genetic and acquired factors. Chronic progressive systemic inflammation caused by RA is closely associated to the inflammatory pathway underlying the pathogenesis of diabetes mellitus. However, most studies to investigate the association have been conducted mainly in foreign countries, and the study results have been inconsistent. Thus, this study attempted to look at the factors affecting both the pre-diabetes stage and the development of diabetes in RA patients in Korea, and also sought to find risk factors for the development. For this purpose, data from RA patients aged 40 to 69 (n=501) were used among the community-based cohort data from the Korean Genome Epidemiology Study of the Korea Disease Control and Prevention Agency. Simple logistic regression was used to investigate factors influencing the development of pre-diabetes and diabetes. As a result, the prevalence of both pre-diabetes and diabetes in RA patients was found to be higher than that in the general population. RA patients’ risk of developing diabetes was higher if they were female, older, less educated, or had a larger waist circumference, higher body mass index, higher blood pressure, lower triglycerides, and lower high-density lipoprotein cholesterol. However, no association between RA and diabetes was found in factors such as marital status, income, occupation, fatigue, sleep time, smoking, and physical activity. The reason why the association was not found in factors such as the physical activity was discussed in the context of statistical errors made in the process of categorizing the raw data. Despite such weaknesses, the significance of this study was that it was an attempt to pursue the association between RA and diabetes based on demographic, physical measurement, and hematologic data.

Snoring-related polygenic risk and its relationship with lifestyle factors in a Korean population: KoGES study

Whereas lifestyle-related factors are recognized as snoring risk factors, the role of genetics in snoring remains uncertain. One way to measure the impact of genetic risk is through the use of a polygenic risk score (PRS). In this study, we aimed to investigate whether genetics plays a role in snoring after adjusting for lifestyle factors. Since the effect of polygenic risks may differ across ethnic groups, we calculated the PRS for snoring from the UK Biobank and applied it to a Korean cohort. We sought to evaluate the reproducibility of the UK Biobank PRS for snoring in the Korean cohort and to investigate the interaction of lifestyle factors and genetic risk on snoring in the Korean population. In this study, we utilized a Korean cohort obtained from the Korean Genome Epidemiology Study (KoGES). We computed the snoring PRS for the Korean cohort based on the UK Biobank PRS. We investigated the relationship between polygenic risks and snoring while controlling for lifestyle factors, including sex, age, body mass index (BMI), alcohol consumption, smoking, physical activity, and sleep time. Additionally, we analyzed the interaction of each lifestyle factor and the genetic odds of snoring. We included 3526 snorers and 1939 nonsnorers from the KoGES cohort and found that the PRS, a polygenic risk factor, was an independent factor for snoring after adjusting for lifestyle factors. In addition, among lifestyle factors, higher BMI, male sex, and older age were the strongest lifestyle factors for snoring. In addition, the highest adjusted odds ratio for snoring was higher BMI (OR 1.98, 95% CI 1.76–2.23), followed by male sex (OR 1.54, 95% CI 1.28–1.86), older age (OR 1.23, 95% CI 1.03–1.35), polygenic risks such as higher PRS (OR 1.18, 95% CI 1.08–1.29), drinking behavior (OR 1.18, 95% CI 1.03–1.35), late sleep mid-time (OR 1.17, 95% CI 1.02–1.33), smoking behavior (OR 0.99, 95% CI 0.82–1.19), and lower physical activity (OR 0.92, 95% CI 0.85–1.00). Our study identified that the UK Biobank PRS for snoring was reproducible in the Korean cohort and that genetic risk served as an independent risk factor for snoring in the Korean population. These findings may help to develop personalized approaches to reduce snoring in individuals with high genetic risk.

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.

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.

Association of long-term hyperglycaemia and insulin resistance with brain atrophy and cognitive decline: A longitudinal cohort study.

To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline. We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Time-weighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits. Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference=-1.96 ml, 95% CI: -3.73, -0.18) and executive function decline (adjusted Z score difference=-0.14, 95% CI: -0.23, -0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group. Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline.

Genetic predisposition according to the age at the onset of atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Ministry of Health and Welfare National Research Foundation of Korea (NRF) Background Although atrial fibrillation (AF) is a heritable disease, multiple comorbid factors, including aging, contribute to its development. Purpose We investigated the association between a weighted genetic risk score (wGRS) for AF and the age at onset. Methods We included 1,968 patients with AF (Yonsei AF Ablation cohort) and 5,486 controls from the Korean Genome Epidemiology Study (KoGES). After 1:1 matching, 1,416 patients and 1,416 controls were included in the analyses. The age of AF onset was determined by the first electrocardiogram (ECG) documentation. Results We selected nine previously reported AF-associated single-nucleotide polymorphisms (SNPs). Among nine proven AF-associated SNPs, 4 genes (PRRX1, PPFIA4, PITX2, and ZFHX3) were independently associated with the age at the onset of AF (p&amp;lt;0.05), but no associated genes were found in the controls. In the quartile and multivariate analyses, the lower quartile age at the onset of AF had a higher wGRS (p&amp;lt;0.001), and a younger age at the onset of AF was independently associated with the wGRS (β -0.29 [-0.57--0.01], p=0.045), but that association was not observed in the control cohort. Contrarily, the higher quartile of the wGRS group had a younger age of AF onset (p&amp;lt;0.001), and the wGRS was independently associated with the age at onset of AF (β -0.02 [-0.03--0.01], p=0.002). In the subgroup analyses, these age-wGRS associations were significant in males (p&amp;lt;0.001) and in those without heart failure (p&amp;lt;0.001) or strokes (p&amp;lt;0.001). Conclusions AF-associated genetic loci significantly contributed to the age at the onset of AF, as determined by the first ECG.

Substitution of Carbohydrates for Fats and Risk of Type 2 Diabetes among Korean Middle-Aged Adults: Findings from the Korean Genome and Epidemiology Study.

Using data from a 16 year follow-up cohort of the Korean Genome Epidemiology Study, this study assessed the effects of carbohydrate intake on incident diabetes, including replacement of fats or proteins with carbohydrates. In addition, this study evaluated modification effects based on 24 genetic variants associated with type 2 diabetes. For the daily intake of macronutrients, the energy-adjusted intake and percentage of total energy intake were calculated. The effects were assessed using a Cox proportional hazards model; results were presented as hazard ratios with 95% confidence intervals (CIs). Among the 7413 participants considered to be diabetes-free at baseline, 1193 individuals were considered to have incident diabetes. The risk of incident diabetes was found to be high at both extremes of carbohydrate intake, with the lowest risk at 78 E%. The replacement of 5 E% intake from fats with isocaloric carbohydrates showed an 11% increase in the risk of diabetes (95% CI: 1.01–1.21), which was significant in men, participants >50 years of age, and participants with a high educational level. Regarding gene–environment interactions, the relationship between carbohydrate intake and incident diabetes was not dependent on genetic variants. A nonlinear relationship was observed between carbohydrate intake and incident diabetes. The substitution of carbohydrates for fats was also associated with an increased risk of incident diabetes.

CLOCK Genetic Variations Are Associated With Age-Related Changes in Sleep Duration and Brain Volume.

Although a connection between sleep disruption and brain aging has been documented, biological mechanisms need to be further clarified. Intriguingly, aging is associated with circadian rhythm and/or sleep dysfunction in a key gene regulating circadian rhythm, Circadian Locomotor Output Cycles Kaput (CLOCK), has been linked to both aging-related sleep disturbances and neurodegenerative diseases. This study aims to investigate how CLOCK genetic variation associates with sleep duration changes and/or volumetric brain alteration. This population-based cross-sectional study used data from the Korean Genome Epidemiology Study and analyzed sleep characteristics and genetic and brain imaging data in 2 221 participants (mean 58.8 ± 6.8 years, 50.2% male). Eleven single-nucleotide polymorphisms (SNPs) in CLOCK were analyzed using PLINK software v1.09 to test for their association with sleep duration and brain volume. Haplotype analysis was performed by using pair-wise linkage disequilibrium of CLOCK polymorphisms, and multivariate analysis of covariance was for statistical analysis. Decreased sleep duration was associated with several SNPs in CLOCK intronic regions, with the highest significance for rs10002541 (p = 1.58 × 10-5). Five SNPs with the highest significance (rs10002541, rs6850524, rs4580704, rs3805151, rs3749474) revealed that CGTCT was the most prevalent. In the major CGTCT haplotype, decreased sleep duration over time was associated with lower cortical volumes predominantly in frontal and parietal regions. Less common haplotypes (GCCTC/CGTTC) had shorter sleep duration and more decreases in sleep duration over 8 years, which revealed smaller total and gray matter volumes, especially in frontal and temporal regions of the left hemisphere. CLOCK genetic variations could be involved in age-related sleep and brain volume changes.

MO575SEX DISPARITY IN THE ASSOCIATION BETWEEN DIETARY SODIUM INTAKE AND THE RISK OF INCIPIENT OSTEOPOROSIS

Abstract Background and Aims Rationale &amp; Objective: Dietary nutrition is closely related with bone health, but there is wide controversy on the association of dietary sodium intake with bone densitometry (BMD) and risk of incipient osteoporosis. Method Study Design: Community-based retrospective cohort study Measurement: We used Tanaka method for estimating 24-h urinary sodium excretion (e24hUNaETanaka) as candidate indicator of dietary sodium intake. Setting &amp; Participants: Using long-term follow-up cohort data from the Korean Genome Epidemiology Study, we identified 4310 participants without osteoporosis and classified them into quartile according to their e24hUNaETanaka. Outcome: Participants were followed up for 12 years of less for a new diagnosis of osteoporosis. Analytical Approach: Multiple Cox-proportional hazard model was performed to estimate hazard ratio (HR) of osteoporosis and survival curve analysis was utilized to compare cumulative survivals. Results Decreased dietary sodium intake was deeply related with low BMD parameters. Multiple Cox-proportional hazard model, adjusted for various conventional risk factors of decreased BMD, demonstrated that e24hUNaETanaka had inverse association with the risk of osteoporosis (adjusted HR = 0.868, 95% CI = 0.768-0.981). Interestingly, our RCS analysis revealed that there was wide variation in the relation between dietary sodium intake and the risk of incipient osteoporosis according to sex and female hormone status: negative curvilinear relationship in male participants; positive linear relationship in premenopausal female participants; and negative linear relationship in postmenopausal female participants. Conclusion Our findings suggest that decreased sodium intake was a significant predictor of osteoporosis progression and there was some sex disparity in the relation dietary sodium intake and the risk of incipient osteoporosis.

Association of pericardial adipose tissue with left ventricular structure and function: a region\u2010specific effect?

BackgroundThe independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity.MethodsWe studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT.ResultsStudy participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P < 0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P < 0.001) and decreased systolic (P = 0.015) and early diastolic (P < 0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted even after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was also the only obesity index independently associated with systolic TDI velocity (P < 0.001).ConclusionsPAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.

Role of arterial stiffness in the association between hand grip strength and cardiovascular events: the Korean Genome and Epidemiology Study.

Hand grip strength (HGS) has been associated with cardiovascular events. However, the exact mechanism responsible for the inverse association between HGS and cardiovascular events has not been established. The aim of this study was to assess whether arterial stiffness mediates this association. We studied 1508 participants (age; 60 ± 5, men; 47.5%) from the Ansan cohort of the Korean Genome Epidemiology Study. Participants were assessed for various parameters of arterial stiffness as well as HGS. The augmentation index (AIx) and brachial-ankle pulse wave velocity (baPWV) were evaluated by using an applanation tonometer and automated waveform analyzer, respectively. Carotid intima medial thickness (IMT) was measured by B-mode ultrasonogram with a 7.5-MHz linear array transducer. HGS was evaluated using a Jamar dynamometer. With increased grip strength, AIx decreased (r = 0.437, P < 0.001). baPWV (r = 0.044, P = 0.107) and carotid IMT (r = 0.005, P = 0.856) had no significant correlation with grip strength. This trend was consistently observed regardless of hypertension, but was more pronounced in participants with hypertension. HGS was significantly correlated with AIx, but not with baPWV and carotid IMT. Our findings suggest that central arterial stiffness could mediate the association between HGS and cardiovascular events.

Genetic Variations in Thiamin Transferase SLC35F3 and the Risk of Hypertension in Koreans.

Hypertension is a major health issues globally. Multiple genetic and environmental factors are involved in hypertension etiology. Solute carrier family 35 member F3 (SLC35F3) is a type of transporter uptakes thiamin across the cellular and mitochondrial membrane. Recent studies suggested that variations in SLC35F3 are associated with the risk of hypertension; however, studies are limited in Koreans. This study examined the association of the genetic variations in SLC35F3 and the risk of hypertension in Koreans using the Korean Genome Epidemiology Study (Ansan/Ansung study). A total of 8,298 Koreans (males 3,983, females 4,315) were analyzed for their general characteristics, dietary intake, and blood pressure. Twenty-four tagging variations in SLC35F3 were selected and investigated for their association with the risk of hypertension using a sex-stratified approach. Findings suggested that, in males, rs12135117 A allele carriers were at the lower risk for hypertension (adjusted odds ratio, 0.859; 95% confidence interval [CI], 0.740–0.998). In females, rs10910387 TC genotype tended to increase the risk 1.172-fold for hypertension (95% CI, 1.002–1.370). Multiple linear regression models exhibited that rs12135117 A allele was negatively associated with blood pressure in males, and rs10910387 TC genotype had a positive association with blood pressure in females. However, statistical significance for these genetically modified effects was in lacked (Bonferroni's corrected p > 0.002). In conclusion, genetic variation in SLC35F3 is not a decisive prediction marker for hypertension risk in Koreans. Given the rarity of data, more studies are required to evaluate the role of SLC35F3 and thiamin in the hypertension etiology.

Independent and interactive associations of season, dietary vitamin D, and vitamin D-related genetic variants with serum 25(OH)D in Korean adults aged 40 years or older.

Only limited information is available on the inter-relationships between genetic and non-genetic factors such as diet and sunlight exposure with serum 25-hydroxyvitamin D [25(OH)D] concentration. This cross-sectional study aimed to examine the independent and interactive associations of season, dietary vitamin D intake, and SNPs of 11 vitamin D-related candidate genes with serum 25(OH)D concentration among 2,721 adults aged ≥40 years at baseline from the Yangpyeong cohort, a part of the Korean Genome Epidemiology Study (KoGES). The interactions between season or dietary vitamin D and 556 SNPs were evaluated using 2-degree of freedom joint tests. Season was strongly (pdifference = 1.00 × 10-12) and dietary vitamin D intake was slightly but significantly associated with serum 25(OH)D concentration (pdifference = 0.0119). Among five SNPs (rs11723621-GC, rs7041-GC, rs10500804-CYP2R1, rs7129781-CYP2R1, and rs2852853-DHCR7) identified in the screening steps, only one, rs10500804-CYP2R1, significantly interacted with season (pinteraction = 8.01 × 10-5). The inverse association between number of minor alleles of rs10500804-CYP2R1 and concentration of 25(OH)D was significant only in summer/fall. Conversely, dietary vitamin D intake was positively associated only in winter/spring. In conclusion, season, dietary vitamin D intake, and four SNPs in GC, CYP2R1, and DHCR7 are independently and rs10500804-CYP2R1 is interactively associated with serum 25(OH)D concentration. Serum 25(OH)D is influenced by genotype of rs10500804-CYP2R1 in summer/fall when sunlight exposure is high, while dietary vitamin D intake is an important determinant of serum 25(OH)D during the seasons with low cutaneous vitamin D synthesis.

Impact of Obesity on Urinary Tract Infections in Korean Adults: Secondary Data Analysis Using Community-Based Cohort Study.

This study investigated the incidence of urinary tract infection (UTI) in community-dwelling adults and identified the association between obesity and UTI. The participants were 4,926 adults aged over 40 years who had no UTIs at the baseline survey of the Korean Genome Epidemiology Study. Obesity was defined according to the cirtieria of Korean Society for the Study of Obesity using body mass index (BMI) data. UTI was defined as those who had self-reported UTI or had either nitrite, or both leukocytes and blood in the urine dipstick test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariate Cox proportional hazards regression analysis to identify the association between the obesity and UTI. The incidence proportion of UTI was 5.1%, and the incidence density per 1,000 person-years was 25.5. After controlling general characteristics, people with BMI ≥30.0 kg/m² remained 1.66 times (HR = 1.66, 95% CI = 1.06~2.60; p < .05) more likely to have UTI than those with normal weight. This trend was also present in men or people aged ≥ 60 years. Among women aged ≥ 60 years, people with BMI ≥ 30.0 kg/m² were 1.98 times (HR = 1.98, 95% CI = 1.01~3.86; p < .05) more likely to have UTI than those with normal weight. The BMI ≥ 30.0 kg/m² is a risk factor of UTIs in Korean adult men over 40 years and women aged ≥ 60 years. It is necessary to emphasize the importance of obesity management to men or women aged ≥ 60 years, specifically.

Genetic variation in CD36 is associated with dietary intake in Korean males.

Fat is one of the six types of taste. Perceived taste intensity could affect the preference for a food and whether or not it is consumed. Cluster of differentiation 36 (CD36) translocates fatty acids on the cellular membrane and is involved in the oral fat-sensing mechanism. Therefore, genetic variation rs1761667 in CD36 is known to be associated with the perception of fat taste and, hence, its dietary intake. This study examined whether CD36 rs1527479 T>C, a proxy of rs1761667, is associated with fat intake and related dietary behaviour in Koreans. Using the data of the Ansan/Ansung Study, a part of the Korean Genome Epidemiology Study, the association of rs1527479 with the intake of macronutrients, including fat and selected foods, and fat-related dietary behaviours were investigated in 3194 males and 3425 females grouped by their degree of obesity. The findings suggested that rs1527479 did not have a meaningful effect on the intake of fat or other macronutrients or on the selection of food among non-obese females and males. However, in males with obesity, the genetic variation showed a significant association with vegetable intake. Obese males with the mutant CC genotype had substantially lower cruciferous vegetable consumption (adjusted P = 0·0015) than individuals with the TT and CT genotypes. Rs1527479 had no significant effect on the frequency of consuming fried foods or commonly used types of seasoning and cooking oils. In conclusion, CD36 genetic variation was associated with the intake of cruciferous vegetables but not fat intake in obese Korean males.

Dietary patterns related to cardiovascular disease based on reduced rank regression analysis of healthy middle-aged Koreans: data from the community-based Korean Genome and Epidemiology Study (KoGES) cohort

Dietary patterns (DPs) provide a comprehensive picture of the foods consumed by an individual. Using 12-y follow-up data from the Korean Genome Epidemiology Study (KoGES), we determined the associations of DPs with incident cardiovascular disease (CVD) using reduced rank regression (RRR). This study analyzed the data of 7354 CVD-free subjects aged 40-69 y drawn from the community-based KoGES cohort. Based on the daily intake of 26 food groups at baseline, we identified DPs based on retinol, vitamin B-2 (riboflavin), and vitamin B-3 (niacin) intakes using RRR. The effects of the DPs on incident CVD were assessed using HRs with 95% CIs. Furthermore, using a marginal structural model, the association between DPs and incident CVD was evaluated after adjusting for time-varying confounders. The incidence of CVD during the follow-up period was 3.7 per 1000 person-years (n=274). The identified DP accounted for 28.99% of the variation in the response variables (i.e., the intake amounts of all 3 nutrients) and was characterized by high intakes of eggs, fish, milk, and dairy products. The effect of DP quintile on incident CVD differed by sex (Pinteraction=0.03); the highest DP quintile was associated with a protective effect against the development of CVD in women (HR: 0.44; 95% CI: 0.22, 0.89), but not in men (HR: 1.57; 95% CI: 0.82, 3.00), compared with the lowest quintile. Even after adjusting for time-dependent variables, the effect of DP on incident CVD was significant in women (HR: 0.43; 95% CI: 0.22, 0.84), but not in men (HR: 1.49; 95% CI: 0.71, 3.10). In this study, we identified DPs related to CVD, and a DP characterized by high intakes of eggs, fish, milk, and dairy products protected against incident CVD in women.

P0770IMPAIRED FASTING GLUCOSE AND CHRONIC KIDNEY DISEASE: A MENDELIAN RANDOMIZATION STUDY

Abstract Background and Aims Diabetes mellitus is a risk factor of chronic kidney disease (CKD); however, the relationship between fasting glucose and CKD remains controversial in non-diabetic population. Method This study included 6,354 participants without diabetes and CKD from the KoreanGenome Epidemiology Study. The genetic risk score (GRS9) was calculated using nine genetic variants associated with fasting glucose in previous genome wide association studies. Incident CKD was defined as estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 or proteinuria (≥1+). The causal relationship between fasting glucose and CKD was evaluated using Mendelian randomization (MR) approach. Results The GRS9 was strongly associated with fasting glucose (β, 1.01; P &amp;lt; 0.001). During a median follow-up of 11.6 years, 531 (8.4%) CKD events occurred. After adjusting for confounding factors, fasting glucose was not associated with incident CKD (odds ratio [OR], 0.991; 95% confidence interval [CI], 0.980–1.003; P =0.139). In the MR analysis, GRS9 was not associated with CKD development (OR per 1 standard deviation increase, 1.179; 95% CI, 0.819–1.696; P = 0.376). Further evaluation with various other MR methods using inverse-variance weighted, MR-Egger, and weighted median methods for multiple genetic variants and strict CKD criteria (decrease in the eGFR of ≥ 30% to a value of &amp;lt; 60 mL/min/1.73m2) found no significant relationship between GRS9 and incident CKD. Conclusion Impaired fasting glucose was not causally associated with CKD development in nondiabetic population.

Impaired fasting glucose and development of chronic kidney disease in non-diabetic population: a Mendelian randomization study

IntroductionDiabetes mellitus is a risk factor of chronic kidney disease (CKD); however, the relationship between fasting glucose and CKD remains controversial in non-diabetic population. This study aimed to assess causal...