Identification of five novel genetic loci related to facial morphology by genome-wide association studies.

BACKGROUND: Face morphology is strongly determined by genetic factors. However, only a small number of genes related to face morphology have been identified to date. Here, we performed a two-stage genome-wide association study (GWAS) of 85 face morphological traits in 7569 Koreans (5643 in the discovery set and 1926 in the replication set). RESULTS: In this study, we analyzed 85 facial traits, including facial angles. After discovery GWAS, 128 single nucleotide polymorphisms (SNPs) showing an association of P < 5 × 10- 6 were selected to determine the replication of the associations, and meta-analysis of discovery GWAS and the replication analysis resulted in five genome-wide significant loci. The OSR1-WDR35 [rs7567283, G allele, beta (se) = -0.536 (0.096), P = 2.75 × 10- 8] locus was associated with the facial frontal contour; the HOXD1-MTX2 [rs970797, A allele, beta (se) = 0.015 (0.003), P = 3.97 × 10- 9] and WDR27 [rs3736712, C allele, beta (se) = 0.293 (0.048), P = 8.44 × 10- 10] loci were associated with eye shape; and the SOX9 [rs2193054, C allele, beta (se) (ln-transformed) = -0.007 (0.001), P = 6.17 × 10- 17] and DHX35 [rs2206437, A allele, beta (se) = -0.283 (0.047), P = 1.61 × 10- 9] loci were associated with nose shape. WDR35 and SOX9 were related to known craniofacial malformations, i.e., cranioectodermal dysplasia 2 and campomelic dysplasia, respectively. In addition, we found three independent association signals in the SOX9 locus, and six known loci for nose size and shape were replicated in this study population. Interestingly, four SNPs within these five face morphology-related loci showed discrepancies in allele frequencies among ethnic groups. CONCLUSIONS: We identified five novel face morphology loci that were associated with facial frontal contour, nose shape, and eye shape. Our findings provide useful genetic information for the determination of face morphology.

Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats.

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

Genome-wide association studies identify locus on 6p21 influencing lung function in the Korean population.

BACKGROUND AND OBJECTIVE: Loss of lung function is an important chronic obstructive pulmonary disease phenotype and decreased forced expiratory volume in 1 s (FEV1) is an independent risk factor of morbidity and mortality. Genome-wide association studies (GWAS) identifying genetic variants underlying lung function have been performed mostly in Caucasian populations. In this study, we aimed to identify genetic variants influencing lung function in a Korean population. METHODS: GWAS on lung function (FEV1 and FEV1/forced vital capacity (FVC) ratio) were performed in two cohort studies. A population-based cohort, the Korean Association Resource phase 3 (KARE3) (6223 subjects), served as a discovery set. The replication analysis was performed in a family-based cohort, the Healthy Twin Study (HTS; 2730 subjects). Dense single-nucleotide polymorphism array data from each study were imputed and used for genetic analysis. RESULTS: At the discovery phase, variants in 6p21 and 17q24 showed the strongest association with FEV1/FVC ratio and FEV1. Several variants in FAM13A on 4q22 locus exhibited positive association with FEV1/FVC ratio. In the replication set, PPT2 in the 6p21 region showed significant association with lung function in the HTS, although the 4q22 locus and the 17q24 locus were not replicated. CONCLUSIONS: We identified that PPT2 on chromosome 6p21 is associated with loss of lung function in the Korean population.

Prevalence of widespread pain and its influence on quality of life: population study in Korea.

The objective of this study was to examine the prevalence and risk factors for widespread pain and its influence on quality of life in residents of Korean communities. A rural and an urban community were selected, and 5,037 subjects were surveyed. Participants were asked if they had pain, aching, or stiffness in any of their joints on most days. Widespread pain was defined as pain above the waist, below the waist, on both sides of the body and in the axial region. The prevalence of widespread pain was 12% (16.2% and 5.5% in females and males, respectively). It was more frequent among females and increased with age in both genders. Age, female gender, and the presence of hand or knee arthritis were significantly associated with widespread pain after multivariate analysis. Except for mental health, all the items in the SF-12 were adversely affected in the widespread pain group after adjustment for confounding factors. Our findings show that the prevalence of widespread pain among residents of Korean communities is comparable to that reported among Caucasians. The significantly worse quality of life among subjects with widespread pain suggests that it may cause major health issues in the aging population.

Identification of 15 loci influencing height in a Korean population.

Height is a complex genetic trait that involves multiple genetic loci. Recently, 44 loci associated with height were identified in Caucasian individuals by large-scale genome-wide association (GWA) studies. To identify genetic variants influencing height in the Korean population, we analyzed GWA data from 8842 Korean individuals and identified 15 genomic regions with one or more sequence variants associated with height (P<1 x 10(-5)). Of these, eight loci were newly identified in Koreans (SUPT3H, EXT1, FREM1, PALM2-AKAP2, NUP37-PMCH, IGF1, KRT20 and ANKRD60). The 15 significant loci account for approximately 1.0% of height variation, with a 3.7-cm difference between individuals with < or =8 height-increasing alleles (5.1%) and > or =19 height-increasing alleles (4.2%). We also examined the associations between height loci and idiopathic short stature (ISS). Five loci (SPAG17, KBTBD8, HHIP, HIST1H1D and ACAN) were significantly associated with ISS (uncorrected P<0.05), indicating that height-associated genes in the adult population are involved in extreme cases of short stature in children. This study validates previous reports of loci associated with human height and identified novel candidate regions involved in human growth and development.

Validation of Risk Prediction Models for Atherosclerotic Cardiovascular Disease in a Prospective Korean Community-Based Cohort.

BACKGROUND: To investigate the performance of the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) in a large, prospective, community-based cohort in Korea and to compare it with that of the Framingham Global Cardiovascular Disease Risk Score (FRS-CVD) and the Korean Risk Prediction Model (KRPM). METHODS: In the Korean Genome and Epidemiology Study (KOGES)-Ansan and Ansung study, we evaluated calibration and discrimination of the PCE for non-Hispanic whites (PCE-WH) and for African Americans (PCE-AA) and compared their predictive abilities with the FRS-CVD and the KRPM. RESULTS: The present study included 7,932 individuals (3,778 men and 4,154 women). The PCE-WH and PCE-AA moderately overestimated the risk of atherosclerotic cardiovascular disease (ASCVD) for men (6% and 13%, respectively) but underestimated the risk for women (-49% and -25%, respectively). The FRS-CVD overestimated ASCVD risk for men (91%) but provided a good risk prediction for women (3%). The KRPM underestimated ASCVD risk for men (-31%) and women (-31%). All the risk prediction models showed good discrimination in both men (C-statistic 0.730 to 0.735) and women (C-statistic 0.726 to 0.732). Recalibration of the PCE using data from the KOGES-Ansan and Ansung study substantially improved the predictive accuracy in men. CONCLUSION: In the KOGES-Ansan and Ansung study, the PCE overestimated ASCVD risk for men and underestimated the risk for women. The PCE-WH and the FRS-CVD provided an accurate prediction of ASCVD in men and women, respectively.

Residential Radon Exposure and Cigarette Smoking in Association with Lung Cancer: A Matched Case-Control Study in Korea.

Residential radon exposure and cigarette smoking are the two most important risk factors for lung cancer. The combined effects thereof were evaluated in a multi-center matched case-control study in South Korea. A total of 1038 participants were included, comprising 519 non-small cell lung cancer cases and 519 age- and sex- matched community-based controls. Residential radon levels were measured for all participants. Multivariate logistic regression was used to calculate odds ratios (OR) for lung cancer according to radon exposure (high ≥ 100 Bq/m3 vs. low < 100 Bq/m3), smoking status, and combinations of the two after adjusting for age, sex, indoor hours, and other housing information. The median age of the participants was 64 years, and 51.3% were women. The adjusted ORs (95% confidence intervals [CIs]) for high radon and cigarette smoking were 1.56 (1.03-2.37) and 2.53 (1.60-3.99), respectively. When stratified according to combinations of radon exposure and smoking status, the adjusted ORs (95% CIs) for lung cancer in high-radon non-smokers, low-radon smokers, and high-radon smokers were 1.40 (0.81-2.43), 2.42 (1.49-3.92), and 4.27 (2.14-8.52), respectively, with reference to low-radon non-smokers. Both residential radon and cigarette smoking were associated with increased odds for lung cancer, and the difference in ORs according to radon exposure was much greater in smokers than in non-smokers.

Estimated Association Between Cytokines and the Progression to Diabetes: 10-year Follow-Up From a Community-Based Cohort.

CONTEXT: The long-term association between multiple cytokines and progression to diabetes is still uncertain. OBJECTIVE: To identify which cytokines could predict progression to prediabetes and type 2 diabetes over 10 years. METHODS: The study included 912 participants aged 40 to 69 years at baseline from the Ansung cohort, part of the Korea Genome Epidemiology Study. At baseline, a 75-g oral glucose tolerance test and 8 cytokines were measured: plasminogen activator inhibitor 1 (PAI-1), resistin, interleukin 6, leptin, monocyte chemoattractant protein 1, tumor necrosis factor alpha, retinol binding protein 4 (RBP4), and adiponectin. People with normal glucose tolerance (NGT, n = 241) and prediabetes (n = 330) were followed-up biennially for 10 years. Multinomial logistic regression analysis was used to evaluate the predictability of cytokines on the new-onset prediabetes and type 2 diabetes. RESULTS: At 10 years, 38 (15.8%) and 82 (34.0%) of those with NGT had converted to prediabetes and type 2 diabetes, respectively. Of those with prediabetes, 228 (69.1%) had converted to type 2 diabetes. In people with NGT or prediabetes at baseline, the highest tertile of RBP4 was associated with a 5.48-fold and 2.43-fold higher risk of progression to type 2 diabetes, respectively. The odds for converting from NGT to prediabetes in the highest tertile of PAI-1 and the lowest tertile of adiponectin were 3.23 and 3.37, respectively. In people with prediabetes at baseline, those in the highest tertile of resistin were 2.94 time more likely to develop type 2 diabetes (all P < 0.05). CONCLUSIONS: In this 10-year prospective study, NGT with higher serum RBP4 and PAI-1, and with lower adiponectin were associated with new-onset prediabetes and type 2 diabetes.

Lactation improves pancreatic ß cell mass and function through serotonin production.

Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on ß cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including ß cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of ß cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased ß cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in ß cells. Secreted serotonin stimulated ß cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved ß cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing ß cell proliferation and reducing oxidative stress in ß cells.

Effect of Blood Pressure on Cardiovascular Diseases at 10-Year Follow-Up.

The American College of Cardiology/American Heart Association (ACC/AHA) recently published a Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. However, the data in other ethnic groups are not well known. We evaluated the prevalence and associated cardiovascular prognosis of Korean subjects with newly reclassified hypertension based on the 2017ACC/AHA guideline. We analyzed data from the Korean Health and Genome Study (n = 10,038). Supine blood pressure (BP) was measured thrice following a standardized protocol and averaged. There was a significant linear relation between BP profiles and cardiovascular disease (CVD)/mortality. Hazard ratio for CVD increased above a systolic BP of 120mm Hg. Systolic BP ≥130mm Hg was significantly associated with increased risk of CVD, coronary heart disease, stroke, CVD death, and total deaths. There was a similar significant linear relation with diastolic BP categories between CVD risk and death. BP is associated with an increased risk of CVD or all-cause mortalities. Moreover, the new BP categories of the 2017ACC/AHA guideline could be applicable for predicting CVD and death in Korean population.

Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus.

The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.

Gender-specific associations between fat mass, metabolic syndrome and musculoskeletal pain in community residents: A three-year longitudinal study.

Increase in fat mass is correlated with musculoskeletal pain. The aim of this study was to examine the relationship between fat mass and the musculoskeletal pain prospectively in Korean community residents. In the Korean Health and Genome Study, participants (mean age 60.2 years, 56.2% women) completed pain questionnaires and underwent dual x-ray absorptiometry to calculate body composition. Three-year follow-up data on pain was available for 1,325 participants. Pain was categorized according to number of pain regions. At three years of follow-up, participants were classified as follows: 1) no pain both at baseline and at three years (no pain), 2) any pain (one, two or more, or widespread regions) at baseline and no pain at three years (transient pain), 3) no pain at baseline and any pain at three years (new pain) 4) any pain both at baseline and at 3 years (persistent pain). 1) and 2) were grouped as no/transient pain group (no pain) and 3) and 4) as new/persistent pain group (pain). Female gender and obesity were two significant factors associated with the persistence or development of pain. Total fat mass and fat:muscle mass ratio were associated with pain among female participants only, and the odds ratios for pain were significantly increased in female participants in the highest quartile of total fat mass and fat muscle ratio after adjustment. In conclusion, both female gender and obesity were two significant factors associated with pain. Fat mass parameters and pain were significantly associated only among females.

Relation of Subclinical Hypothyroidism is Associated With Cardiovascular Events and All-Cause Mortality in Adults With High Cardiovascular Risk.

The aim of this study was to determine the association between subclinical hypothyroidism and cardiovascular (CVD) events, and mortality using the atherosclerotic CVD risk score. We carried out an observational study in a prospective cohort that was followed up for 12 years. The study included 3,021 participants aged ≥ 40 years at baseline from the Ansung cohort, part of the Korean Genome and Epidemiology Study. Cox regression models were constructed to evaluate the hazards ratio (HR) and 95% confidence interval (CI) for all-cause mortality and CVD events in groups classified according to thyroid status. Subgroup analysis was performed with a cut-off age of 65 years or 7.5% of the 10-year atherosclerotic CVD risk score. The subclinical hypothyroidism group in the highest quartile of thyroid-stimulating hormone (>6.57 mIU/L) had a significantly increased risk of all-cause mortality (HR 2.12, 95% CI 1.27 to 3.56) and CVD events (HR 1.92, 95% CI 1.21 to 3.04) compared with euthyroid participants. Subgroup analysis by CVD risk revealed that participants with high CVD risk only had a high risk of all-cause mortality (HR 2.18, 95% CI 1.22 to 3.87) and CVD events (HR 2.42, 95% CI 1.35 to 4.33). Further analysis showed that participants aged <65 years with high CVD risk had the highest risk of all-cause mortality (HR 3.50, 95% CI 1.50 to 8.16) and CVD events (HR 3.37, 95% CI 1.46 to 9.57). Our results demonstrated that high thyroid-stimulating hormone levels were associated with a greater risk of mortality and new CVD risks, particularly among subjects with high CVD risk.

Association of Hyperthyroidism and Thyroid Autoantibodies with Moyamoya Disease and Its Stroke Event: A Population-based Case-control Study and Meta-analysis.

The aim of this study was to investigate the specific thyroid condition and thyroid autoantibodies in adult moyamoya disease (MMD) according to clinical presentation (ischemia vs. hemorrhage stroke). In addition, a meta-analysis was performed to reveal the association between adult MMD and elevated thyroid function, or autoantibodies. Prospectively collected data on 169 consecutive patients with MMD at a single institution were analyzed. Community-based controls matched for age and sex were selected for comparison. Penalized multinomial logistic regression analysis was used for factors affecting stroke. For meta-analysis, heterogeneity was evaluated by using the I2 test. If I2 < 50%, a fixed effect model was used. Fifty-four cases (32.0%) presented with ischemic stroke and 37 cases (21.9%) with hemorrhage stroke. Hyperthyroidism had a marginally increased risk of MMD with ischemic stroke with reference value of MMD without stroke [odds ratio (OR), 2.53; P = 0.055]. Anti-thyroperoxidase antibody (TPOAb) increased the risk of MMD presenting with ischemic stroke significantly (OR, 2.99; P = 0.020). A meta-analysis revealed that adult MMD was significantly associated with elevated autoantibodies (OR, 7.663; P = 0.002) and hyperthyroidism (OR, 10.936; P < 0.001). Elevated TPOAb and hyperthyroidism may play important roles in adult MMD with ischemic stroke. Studies focusing on targeted hyperthyroidism and thyroid autoantibodies are necessary in treating adult MMD patients in the future.

Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer.

Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of differentiated thyroid cancer (DTC) were identified by previous genome-wide association studies (GWASs) in Europeans only. Here we conducted a GWAS and a replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls, and validated these results using expression quantitative trait loci (eQTL) analysis and clinical phenotypes. The most robust associations were observed in the NRG1 gene (rs6996585, P=1.08 × 10-10) and this SNP was also associated with NRG1 expression in thyroid tissues. In addition, we confirmed three previously reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC. Furthermore, we identified specific variants of DTC that have different effects according to cancer type or ethnicity. Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations.

Association of Sasang Constitutional Types with Incident Hypertension: A 12-Year Follow-Up Study.

OBJECTIVES: Sasang constitutional types (SCTs) are four distinct classifications of people based on physiologic and physical characteristics. The different types have been reported to have different disease susceptibility, but there are no studies reporting the association of SCT and hypertension (HTN) over a long-term follow-up period. This study prospectively investigated the association between SCT and incidence of HTN. DESIGN: This was a prospective study in a population-based cohort study in Korea. SUBJECTS: Data from two independent population-based cohorts that are embedded within the Korean Genome and Epidemiology Study were used. A total of 2083 subjects who were free of HTN at baseline were selected for the analysis. OUTCOME MEASURES: HTN was diagnosed as systolic blood pressure (BP) ≥140 mmHg and diastolic BP ≥90 mmHg, use of antihypertensive medication, or diagnosis by doctor. The SCTs were classified using an integrated diagnostic method that included facial features, body shape, voice, and questionnaire responses. The association between the SCT and the incidence of HTN was investigated by Cox proportional hazard regression analysis and calculation of estimated survival functions. RESULTS: The Tae-eum (TE) type showed a significantly increased risk for HTN (hazard ratio [HR] = 1.55, 95% confidence interval [CI] 1.15-2.10; p = 0.005), even after adjusting for all possible confounders. In a stratified analysis by body mass index (BMI) conducted only in the TE type, even those in the TE type with normal BMI had a significantly higher risk for HTN (HR = 1.47, 95% CI 1.07-2.03; p = 0.016). Furthermore, survival analysis showed that the TE type had a higher rate of developing HTN than the So-eum and So-yang types had, regardless of obesity status. CONCLUSIONS: These results show that the TE type is an independent risk factor for HTN. Thus, early prevention and treatment for HTN in this type are needed.

Osteoporotic Fracture Risk Assessment Using Bone Mineral Density in Korean: A Community-based Cohort Study.

BACKGROUND: Fracture-risk assessment tool (FRAX) using just clinical risk factors of osteoporosis has been developed to estimate individual risk of osteoporotic fractures. We developed prediction model of fracture risk using bone mineral density (BMD) as well as clinical risk factors in Korean, and assessed the validity of the final model. METHODS: To develop and validate an osteoporotic FRAX, a total of 768 Korean men and women aged 50 to 90 years were followed for 7 years in a community-based cohort study. BMD as well as clinical risk factors for osteoporotic fracture including age, sex, body mass index, history of fragility fracture, family history of fracture, smoking status, alcohol intake, use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis were assessed biannually. RESULTS: During the follow-up period, 86 osteoporotic fractures identified (36 in men and 50 in women). The developed prediction models showed high discriminatory power and had goodness of fit. CONCLUSIONS: The developed a Korean specific prediction model for osteoporotic fractures can be easily used as a screening tool to identify individual with high risk of osteoporotic fracture. Further studies for validation are required to confirm the clinical feasibility in general Korean population.

Risk of the Development of Diabetes and Cardiovascular Disease in Metabolically Healthy Obese People: The Korean Genome and Epidemiology Study.

The reported effects of a metabolically healthy obese (MHO) phenotype on diabetes and cardiovascular disease (CVD) risk are contradictory. Within the context of a population-based cohort study, we aimed to investigate the long-term risk of an MHO status for the development of diabetes and CVD, and whether consistency of this phenotype or age affected cardiometabolic outcomes. We recruited 7588 subjects without diabetes or CVD, aged 40 to 69 years at baseline examination, from the Korean Genome and Epidemiology Study, and followed-up these subjects for 10 years biennially. Participants were divided into 4 groups based on the body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). We defined persistent phenotypes if subjects maintained the same phenotype at every visit from baseline to their last visit. Incident diabetes and CVD morbidity or mortality were identified during 10 years of follow-up. Compared to MHNW controls, MUNW and MUO groups had increased risk for development of diabetes (hazard ratio [HR] 3.0 [95% CI: 2.5-3.6], and 4.0 [3.4-4.7], respectively) and CVD (HR 1.6 [1.3-2.0], and 1.9 [1.5-2.4], respectively). However, the MHO group showed only a marginal increase in risk for diabetes and CVD (HR 1.2 [0.99-1.6], 1.4 [0.99-1.8], respectively). The impact of MHO on the development of diabetes was more prominent in younger individuals (HR 1.9 [1.2-3.1] vs 1.1 [0.8-1.4], <45 years vs ≥45 years at baseline). Only 15.8% of MHO subjects maintained the MHO phenotype at every visit from baseline to the 5th biennial examination (persistent MHO). In subjects with persistent MHO, the risk for diabetes and CVD was significantly higher than those with persistent MHNW (1.9 [1.2-3.1], 2.1 [1.2-3.7], respectively). MHO phenotype, even if maintained for a long time, was associated with a significantly higher risk for the development of diabetes and CVD in Korean subjects.

Genomic epidemiology cohorts in Korea: present and the future.

Human genome epidemiology involves the application of genetic technology to assess the impact of variations at the DNA level on health and disease. Recent developments in molecular biology allow epidemiologists to use biomarkers to determine an individuals predisposition to disease and to detect disease at an early stage. Moreover, advances in genomics and proteomics could play a central role in research into disease prediction and prevention. Large scale population-based cohort prospective studies offer the most comprehensive approach to the delineation of gene function, the effects of the environment, and their interactions. The Korean Multi-center Cancer Cohort (KMCC), under construction since 1993, is the first multi-center prospective cohort to identify risk factors for cancer in Korea. Data on general lifestyle, physical activity, diet, reproductive factors, and agricultural exposure are obtained through direct interview using a structured questionnaire. Anthropometric measurements and clinical laboratory findings are also collected using a web-based data entry system. Moreover, biological materials have been banked [blood (serum, plasma, buffy coat, packed erythrocytes) is stored at -70 degrees C and urine at -20 degrees C] for future analysis. Several other cohorts including the Korean National Cancer Center (KNCC) Cohort, the Korean Health Examinees (KOEX) Cohort, the Korean Health and Genome Epidemiologic Study (KHGES), and the Yang Pyeong Cohort have also been launched since the KMCC cohort was initiated. Even though these cohorts have collected similar data and biospecimen, questionnaires and protocols used have not been standardized. However, these cohort studies are of increased scope and have been designed to detect risk factors for cardiovascular disease, metabolic syndrome, and cancer. Subjects have been followed up actively by health personnel in different regions and by using record linkages with the central cancer registry, and the national death certificate and national health insurance claim databases. As of August 2004, the total number of subjects enrolled in all cohorts with archived biologic specimens was around 80,000. A new genomic cohort has been launched since 2001 in Korea, for which the target number of subjects is 250,000 men and women over the next 5 years. This article describes the goals and the designs of each of the above-mentioned cohorts.

Relationships between body mass index, fat mass, muscle mass, and musculoskeletal pain in community residents.

OBJECTIVE: To evaluate the relationships between fat mass, muscle mass, fat:muscle mass ratio, metabolic syndrome, and musculoskeletal pain in community residents. METHODS: In the Korean Health and Genome Study, 1,530 participants (mean ± SD age 60.8 ± 8.60 years) completed pain questionnaires and underwent dual x-ray absorptiometry to calculate body composition. Pain was categorized according to the number of pain regions, such that widespread pain, defined as pain above the waist, below the waist, on both sides of the body, and in the axial region, represented the most severe pain. Metabolic syndrome was defined using the International Diabetes Federation 2005 recommendations, and the association between metabolic syndrome and pain was evaluated by dividing the population into 4 groups, according to the presence/absence of metabolic syndrome and of high body mass index (BMI). RESULTS: Total fat mass and fat:muscle mass ratio were significantly and positively associated with musculoskeletal pain among female subjects only. Compared to the lowest quartile of fat:muscle mass ratio, the odds ratios for widespread pain among subjects in other quartiles were significantly increased after adjustment for confounders. Widespread pain was more prevalent among subjects with metabolic syndrome whether their BMI was high or normal, especially among female subjects. CONCLUSION: Increased fat mass and fat:muscle mass ratio were significantly associated with musculoskeletal pain among women. Widespread pain was significantly associated with a high fat:muscle mass ratio after adjustment for confounders. Understanding the relationship between fat mass and pain may provide insights into preventative measures and therapeutic strategies for musculoskeletal pain.