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

BACKGROUND: The 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. METHODS: We 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. RESULTS: Study 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). CONCLUSIONS: PAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.

Sleep structure and electroencephalographic spectral power of middle-aged or older adults: Normative values by age and sex in the Korean population.

The fine structure of sleep electrocortical activity reflects health and disease. The current study provides normative data for sleep structure and electroencephalography (EEG) spectral power measures derived from overnight polysomnography (PSG) and examines the effect of age and sex among Korean middle-aged and older adults with or without obstructive sleep apnea (OSA). We analysed home PSG data from 1,153 adult participants of an ongoing population-based cohort study, the Korean Genome and Epidemiology Study. Sleep stages were visually scored and spectral power was measured on a single-channel EEG (C4-A1). We computed spectral power for five frequency ranges. The EEG power was reported in relative (%) and log-transformed absolute values (µV2 ). With ageing, the proportion of N1 sleep increased, whereas N3 decreased, which is more noticeable in men than in women. The amount of N3 was relatively low in this cohort. With ageing, relative delta power decreased and alpha and sigma power increased for the whole sleep period, which was more pronounced during REM sleep in non-OSA. For men compared with women, relative theta power was lower during REM and sigma and beta were higher during N1 sleep. The differences of relative powers by age and sex in OSA were comparable to those in non-OSA. In a community-based Korean population, we present normative data of sleep structure and spectral power for middle-aged or older adults of a non-Caucasian ethnicity. The values varied with age and sex and were not influenced by sleep apnea.

Obesity and muscle may have synergic effect more than independent effects on brain volume in community-based elderly.

OBJECTIVE: To evaluate the individual and combined effects of obesity and muscle mass on brain volume in a community-dwelling healthy older population. METHODS: One thousand two hundred nine participants (M:F = 574:635, mean age 63.6 ± 6.9 years) were included. The cross-sectional area of visceral fat (VF), the height-adjusted appendicular skeletal muscle mass (ASM/height2), and the ratio of thigh muscle to visceral fat (TM/VF) represented obesity, muscle mass, and their integrated value, respectively. Linear regression analysis was performed to establish associations between 215 brain compartment volumes and VF, ASM/height2, and TM/VF after adjusting for covariates. RESULTS: On regression analysis, TM/VF had a positive correlation to the volumes of temporal lobe and cerebellum. TM/VF was associated with volumes of 10 subcompartments. TM/VF was positively correlated with the volumes of left entorhinal cortex, right temporal pole and inferior temporal gyrus related to cognition (p < 0.05, respectively), and the volumes of cerebellum and right pallidum related to movement (p < 0.05, respectively). However, VF had a negative correlation to temporal lobe volume and ASM/height2 had no significant correlation to any of the brain lobes. VF and ASM/height2 were correlated with volumes of 5 subcompartments and one subcompartment, respectively, CONCLUSIONS: TM/VF reflects the integrated effect of obesity and muscle mass and is associated with the volume of more brain regions compared to indices of obesity or muscle mass alone. The positive effect of muscle mass and the negative effect of obesity change the volumes of brain regions related to cognition and movement which were not significantly affected by obesity or muscle mass alone. KEY POINTS: • If obesity and muscle mass were considered together, we could find more significant brain volume changes which were not found in obesity or muscle alone. • The ratio of thigh muscle to visceral fat was positively correlated with the volumes of entorhinal cortex, temporal pole, and inferior temporal gyrus related to cognition. • The ratio of thigh muscle to visceral fat was positively correlated with the volumes of cerebellum and pallidum related to movement.

Paravertebral Muscles as Indexes of Sarcopenia and Sarcopenic Obesity: Comparison With Imaging and Muscle Function Indexes and Impact on Cardiovascular and Metabolic Disorders.

OBJECTIVE. The objectives of this study were to propose the use of the cross-sectional area of paravertebral muscle (PMA) and the ratio of the PMA to the cross-sectional area of visceral fat (PVR) as new indexes of sarcopenia or sarcopenic obesity through comparison with existing indexes and to show the clinical associations of PMA and PVR with hypertension and diabetes. SUBJECTS AND METHODS. A total of 1270 participants (608 men and 662 women; mean [± SD] age, 63.57 ± 6.94 years) were recruited from a community-based population of elderly individuals. PMA and PVR were measured on single-slice abdominal CT images. Pearson correlation was used to evaluate the correlation of PMA and PVR with widely used imaging and muscle function indexes of sarcopenia and sarcopenic obesity. Tertile categories of PMA and PVR were evaluated to investigate associations with risks for hypertension and diabetes in men and women, by use of separate multivariable logistic regression models. RESULTS. PMA was correlated with the cross-sectional area of thigh muscle on CT, appendicular skeletal muscle mass (ASM) on dual-energy x-ray absorptiometry, height-adjusted ASM (calculated as ASM divided by the height in meters squared), and body mass index (BMI)-adjusted ASM (calculated as ASM divided by BMI) (p < .01). PMA was also correlated with hand grip strength and gait speeds (p < .01). PVR was correlated with height-adjusted ASM and BMI-adjusted ASM (p < .01). A high PVR significantly decreased the odds ratios for hypertension and diabetes in the unadjusted model and the model adjusted for age, smoking, and drinking status. The ratio of the cross-sectional area of thigh muscle to the cross-sectional area of visceral fat and the BMI-adjusted ASM produced results similar to those of PVR in terms of the odds ratios for hypertension and diabetes. CONCLUSION. Single-slice abdominal CT can supply PMA and visceral fat information together. PMA and PVR were found to be reliable indexes of sarcopenia and sarcopenic obesity. A high PVR was associated with low risks for hypertension and diabetes.

Relationship of obstructive sleep apnoea severity and subclinical systemic atherosclerosis.

Obstructive sleep apnoea (OSA) is a common form of sleep disordered breathing. Untreated OSA might accelerate atherosclerosis, potentially increasing the cardiovascular disease burden in patients. The present study aimed to evaluate the association between objectively measured OSA severity and the presence of subclinical systemic atherosclerosis using noninvasive measurements, including tomographic quantification of the calcium burden.A total of 2157 participants of the Korean Genome and Epidemiology Study, who were free of structural heart disease and underwent both in-home polysomnography and chest computed tomography, were cross-sectionally analysed. Participants were divided into three groups based on the severity of OSA: no OSA (apnoea-hypopnoea index (AHI) <5 events·h-1, n=1096), mild OSA (AHI 5- <15 events·h-1, n=700) and moderate-to-severe OSA (AHI ≥15 events·h-1, n=361). Calcium deposits in the thoracic aorta and coronary arteries were measured by the Agatston score.Participants with moderate-to-severe OSA were 1.6 times (95% CI 1.18-2.15 times; p=0.002) more likely to have ascending thoracic aorta calcification (≥100 units) than those without OSA, after adjustment for cardiovascular risk factors. In addition, the association between moderate-to-severe OSA and ascending thoracic aorta calcification of subjects with higher epicardial fat volume was slightly stronger than that in patients without OSA and in the lowest epicardial fat volume tertile (OR 2.11, 95% CI 1.30-3.43).Severity of OSA in the general population was independently associated with subclinical systemic atherosclerosis. These findings highlight the potential importance of severe OSA, especially in subjects with higher epicardial fat, as a possible predictive factor for systemic atherosclerosis and cardiovascular disease.

Neck Circumference and Cerebral Gray Matter Volume.

BACKGROUND: While obesity is linked with brain atrophy and dementia incidence, associations with regional adiposity are uncertain. Our goal was to determine whether cerebral gray matter volume is related to neck circumference (NC), a measure of regional adiposity having unique relationships with metabolic disorders and cardiovascular disease. METHODS: Magnetic resonance imaging and NC were cross-sectionally assessed from 2011 to 2014 in a population-based sample of 2916 men and women in the Korean Genome and Epidemiology Study. RESULTS: For men, NC was inversely associated with total and regional gray matter in the frontal, temporal, and occipital lobes after adjusting for age and intracranial brain volume. Associations were especially strong in the presence of diabetes. With further adjustment for indices of body composition and other characteristics, total and frontal gray matter in diabetic men were lowered by 6.1 mL (95% confidence interval: 2.5-9.7, P=0.004) and 2.9 mL (95% confidence interval: 1.0-4.9, P=0.017), respectively, per SD increase in NC (2.3 cm). For men without diabetes, and in all women, associations were less apparent. CONCLUSIONS: In men with diabetes, NC was inversely associated with cerebral gray matter volume. The link between neck anthropometry and brain aging in diabetic men warrants further consideration.

Prevalence and Characteristics of Restless Legs Syndrome in Korean Adults: A Study in Two Independent Samples of the General Population.

BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder, although it has a low prevalence in Asian populations. However, the reported RLS prevalence in -Korean adults is mostly 4.5-12.1%, which is higher than that reported in other Asian populations. This study aimed to diagnose RLS and exclude mimicking conditions in 2 independent samples of Korean adults, and to compare its prevalence to that from previous studies performed in Asian countries. METHODS: Study populations included a (1) nationwide stratified random sample (n = 2,824; age 19-79 years) and (2) community-based cohort (n = 2,685; age 47-79 years). We applied the Cambridge-Hopkins diagnostic questionnaire to diagnose RLS and differentiate it from RLS mimics. Sleep-related symptoms, mood, and medical conditions were compared between the RLS and non-RLS groups. Prior studies of the RLS prevalence in Asia were systematically reviewed and compared to our findings. RESULTS: The adjusted RLS prevalence was 0.4 and 1.3% in populations 1 and 2, respectively. In both populations, subjects with RLS had more depression. The prevalence of RLS mimics was 5.1 and 2.6%, in populations 1 and 2, respectively. The RLS prevalence in Asia was higher when RLS was defined by the presence of essential clinical features and lower when a differential diagnosis was additionally implemented. CONCLUSIONS: The RLS prevalence in Korean adults considering RLS mimics is comparable to that in adults from other Asian countries (< 2%). The reported RLS prevalence varies depending on the diagnostic method employed.

Increased risk for new-onset hypertension in midlife male snorers: The 14-year follow-up study.

While the association between sleep-related breathing disorders such as snoring and hypertension has been well established, it still remains unclear whether the association differs by age and gender. Therefore, in this 14-year follow-up study, we examined the independent association between self-reported snoring and the incidence of hypertension by gender and age groups in a large cohort of Korean adults. A total of 4,954 adults, aged 40-69 years, free of hypertension at baseline were enrolled. Participants were divided into three groups based on a self-reported snoring frequency: never; occasional (snoring <4 nights per week); and habitual snorer (snoring ≥4 nights). At baseline and biennial follow-up visits, blood pressure was measured by trained examiners. Incident hypertension was defined as the first occurrence at any follow-up examination where the participants had blood pressure ≥140/90 mmHg or were being treated with antihypertensive medication. After adjusting for known cardiovascular risk factors, only in men aged ≤45 years was habitual snoring significantly associated with a 1.5 times higher risk for incident hypertension than never snoring. In this age group, habitual snoring was significantly associated with increased risk for the development of hypertension, regardless of the presence of excessive daytime sleepiness. In women, snoring was not significantly associated with hypertension incidence in any age group. The present study suggests that young male snorers may be at high risk for the future development of hypertension, which has important clinical implications for early detection and treatment of snoring to reduce the burden of cardiovascular disease.

Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans.

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

Common variants in DRD2 are associated with sleep duration: the CARe consortium.

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.

Subclinical left ventricular diastolic dysfunction and incident type 2 diabetes risk: the Korean Genome and Epidemiology Study.

BACKGROUND: Subclinical left ventricular (LV) diastolic dysfunction in type 2 diabetes (T2D) is a common finding and represents an early sign of diabetic cardiomyopathy. However, the relationship between LV diastolic dysfunction and the incident T2D has not been previously studied. METHODS: A total of 1817 non-diabetic participants (mean age, 54 years; 48% men) from the Korean Genome and Epidemiology Study who were free of cardiovascular disease were studied. LV structure and function were assessed by conventional echocardiography and tissue Doppler imaging. Subclinical LV diastolic dysfunction was defined using age-specific cutoff limits for early diastolic (Em) velocity, mitral E/Em ratio, and left atrial volume index. RESULTS: During the 6-year follow-up period, 273 participants (15%) developed T2D. Participants with incident T2D had greater LV mass index (86.7 ± 16.4 vs. 91.2 ± 17.0 g/m2), worse diastolic function, reflected by lower Em velocity (7.67 ± 1.80 vs. 7.47 ± 1.70) and higher E/Em ratio (9.19 ± 2.55 vs. 10.23 ± 3.00), and higher prevalence of LV diastolic dysfunction (34.6 vs. 54.2%), compared with those who did not develop T2D (all P < 0.001). In a multivariate logistic regression model, lower Em velocity (odd ratio [OR], 0.867; 95% confidence interval [CI] 0.786-0.957) and the presence of LV diastolic dysfunction (OR, 1.617; 95% CI 1.191-2.196) were associated with the development of T2D, after adjusting for potential confounding factors. CONCLUSIONS: In a community-based cohort, the presence of subclinical LV diastolic dysfunction was a predictor of the progression to T2D. These data suggest that the echocardiographic assessment of LV diastolic function may be helpful in identifying non-diabetic subjects at risk of incident T2D.

Objective snoring time and carotid intima-media thickness in non-apneic female snorers.

Controversy persists about whether snoring can affect atherosclerotic changes in adjacent vessels, independently of obstructive sleep apnea and other cardiovascular risk factors. This study examined the independent association between snoring and carotid artery intima-media thickness (IMT) in non-apneic snorers and non-snorers. We studied 180 non-apneic snorers and non-snorers participating in a full-night home-based sleep study. Snoring sound was measured objectively by a microphone. Based on snoring time across the night, participants were classified as non-snorers (snoring time: 0%), mild snorers (1-25%) and moderate to heavy snorers (≥25%). We measured IMT on both common carotid arteries. The three groups were matched by age, body mass index, cholesterol, blood pressure and glucose levels, using weights from generalized boosted-propensity score models. Mean carotid IMT increased with increased snoring time across the night in women: non-snorers (0.707 mm), mild (0.718 mm) and moderate to heavy snorers (0.774 mm), but not in men. Snoring during at least one-fourth of a night's sleep is associated independently with subclinical changes in carotid IMT in women only.

Cognitive performance norms from the Korean genome and epidemiology study (KoGES).

BACKGROUND: While normative data on neuropsychological performance provide baseline metrics for the assessment and diagnosis of mild cognitive impairment and dementia, a lack of comparative normative data in non-Caucasian populations makes it difficult to conduct similar evaluations and studies in individuals from diverse backgrounds. The current paper aims to provide normative data on a range of cognitive measures in a Korean general population sample and investigate various demographic and health variables associated with cognitive performance in this representative population. METHOD(S): The study population was 1,528 stroke and dementia-free individuals who participated in the Korean Genome and Epidemiology study (KoGES) (mean age 60.43 ± 7.30, 52.42% female). All participants underwent a comprehensive neuropsychological test battery that included verbal and visual memory, language, attention, and executive function measures. A health examination and a questionnaire-based interview were also administered. RESULTS: The majority of cognitive test results were associated with age, education, and gender. In general, higher education and younger age was associated with better cognitive performance. Explained variance increased modestly in models that included measures of general health and depressive symptoms. CONCLUSION: Normative data of cognitive performance in a community based Korean population are presented. These norms provide reference values in a non-Caucasian middle to older aged sample.

Sasang constitutional types for the risk prediction of metabolic syndrome: a 14-year longitudinal prospective cohort study.

BACKGROUND: To examine whether the use of Sasang constitutional (SC) types, such as Tae-yang (TY), Tae-eum (TE), So-yang (SY), and So-eum (SE) types, increases the accuracy of risk prediction for metabolic syndrome. METHODS: From 2001 to 2014, 3529 individuals aged 40 to 69 years participated in a longitudinal prospective cohort. The Cox proportional hazard model was utilized to predict the risk of developing metabolic syndrome. RESULTS: During the 14 year follow-up, 1591 incident events of metabolic syndrome were observed. Individuals with TE type had higher body mass indexes and waist circumferences than individuals with SY and SE types. The risk of developing metabolic syndrome was the highest among individuals with the TE type, followed by the SY type and the SE type. When the prediction risk models for incident metabolic syndrome were compared, the area under the curve for the model using SC types was significantly increased to 0.8173. Significant predictors for incident metabolic syndrome were different according to the SC types. For individuals with the TE type, the significant predictors were age, sex, body mass index (BMI), education, smoking, drinking, fasting glucose level, high-density lipoprotein (HDL) cholesterol level, systolic and diastolic blood pressure, and triglyceride level. For Individuals with the SE type, the predictors were sex, smoking, fasting glucose, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level, while the predictors in individuals with the SY type were age, sex, BMI, smoking, drinking, total cholesterol level, fasting glucose level, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level. CONCLUSIONS: In this prospective cohort study among 3529 individuals, we observed that utilizing the SC types significantly increased the accuracy of the risk prediction for the development of metabolic syndrome.

Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean population by genome-wide association studies including gene-environment interactions.

Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial disease. Although smoking is a main risk factor for obstructive impairment, not all smokers develop this critical disease. We conducted a genome-wide association study to identify the association between genetic variants and pulmonary function and also examined how these variants relate to lung impairment in accordance with smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319) and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we analyzed the association between genetic variants (single-nucleotide polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using multivariate linear regression models. Similar analyses were conducted after stratification by smoking status. Four genome-wide significant signals in the FAM13A gene (the strongest signal at rs2609264, P=1.76 × 10(-7) in a combined set) were associated with FEV1/FVC. For the association with ratio, the effect size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 × 10(-7)) as compared with the TCAG haplotype (reference haplotype) in a combined set. There was also a significant interaction of FAM13A haplotypes with heavy smoking on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes also interacted with heavy smoking to affect the risk of reduced pulmonary function.

GWA meta-analysis of personality in Korean cohorts.

Personality is a determinant of behavior and lifestyle that is associated with health and human diseases. Despite the heritability of personality traits is well established, the understanding of the genetic contribution to personality trait variation is extremely limited. To identify genetic variants associated with each of the five dimensions of personality, we performed a genome-wide association (GWA) meta-analysis of three cohorts, followed by comparison of a family cohort. Personality traits were measured with the Revised NEO Personality Inventory for the five-factor model (FFM) of personality. We investigated the top five single-nucleotide polymorphisms (SNPs) for each trait, and revealed the most highly association with neuroticism and TACC2 (rs1010657, P=8.79 × 10(-7)), extraversion and PTPN12 (rs12537271, P=1.47 × 10(-7)), openness and IMPAD1 (rs16921695, P=5 × 10(-8)), agreeableness and RPS29 (rs8015351, P=1.27 × 10(-6)) and conscientiousness and LMO4 (rs912765, P=2.91 × 10(-6)). It had no SNP reached the GWA study threshold (P<5 × 10(-8)). When expanded the SNPs up to top 100, the correlation of PTPRD (rs1029089) and agreeableness was confirmed in Healthy Twin cohort with other 13 SNPs. This GWA meta-analysis on FFM personality traits is meaningful as it was the first on a non-Caucasian population targeted to FFM of personality traits.

Non-alcoholic fatty liver disease among sasang constitutional types: a population-based study in Korea.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is highly prevalent in populations with metabolic conditions such as obesity and type II diabetes. Specific types of Sasang constitution can act as a risk factor for metabolic diseases, but there are no studies addressing the association between the Sasang constitutional types (SCTs) and NAFLD. METHODS: A total of 1184 individuals (508 males, 676 females) that enrolled in the Korean Genome and Epidemiology Study were included in the present study. Classification of SCTs was done with an integrated diagnostic model. NAFLD was diagnosed when the liver attenuation index (LAI) value was <5 Hounsfield units using computed tomography. Relationships between the SCTs and NAFLD were analyzed using multiple logistic regressions. RESULTS: The average LAI was 13.3±6.0 in the So-eum (SE) type, 12.3±7.0 in the So-yang (SY) type, and 6.5±9.9 in the Tae-eum (TE) type. Prevalence of NAFLD was 4.7% in the SE type, 14.0% in the SY type, and 34% in the TE type. Even after adjusting for possible confounders, the SY and TE types continued to show a 3.90-fold (95% CI, 1.60-9.51; P=0.0028) and 3.36-fold (95% CI, 1.42-7.92; P=0.0057) increase in chance of having NAFLD, respectively, compared with the SE type. In the additional analysis including only non-obese subjects, the odds ratio of NAFLD was 3.27 (95% CI, 1.29-8.29; P=0.0126) in the SY type and 3.53 (95% CI, 1.30-9.58; P=0.0134) in the TE type compared with SE type. In the multivariate analysis to determine which parameter had an independent association with NAFLD, higher body mass index, alanine aminotransferase (ALT), triglyceride (TG), and low high-density lipoprotein cholesterol were independently associated with developing NAFLD in the SY type. In contrast, male sex, alcohol consumption, higher ALT, TG, and fasting glucose were risk factors for NAFLD in the TE type. CONCLUSIONS: These results indicated that the SY and TE types are independent risk factors for NAFLD.

Quantitative analysis of lungs and airways with CT in subjects with the chronic obstructive pulmonary disease (COPD) candidate FAM13A gene: case control study for CT quantification in COPD risk gene.

OBJECTIVE: To investigate the relationship between a chronic obstructive pulmonary disease (COPD) candidate gene, based on a genomewide association study, and computed tomographic (CT) quantitative analysis; and to find a phenotype in the COPD candidate FAM13A gene. MATERIALS AND METHODS: This study was conducted in subclinical male smokers between 2 groups with matched age and smoking status; 162 subjects (mean age, 58 years) with risk (CTGA, n = 85) and reference (TCAG, n = 77) diplotypes replicated through genomewide association study underwent chest CT for quantitative analysis of lungs and airways. We analyzed the measures in both the risk and reference groups using a 2-sample t test. RESULTS: Subjects with the risk CTGA diplotype had significantly higher total lung volume and emphysema index than the reference TCAG diplotype (P = 0.04). Mean lung density was significantly lower (P < 0.05) in the risk group. However, in the analysis of airways, wall area, luminal area, wall and lumen area ratio, and mean lung density on expiratory and inspiratory phases, no significant differences between the 2 groups were seen. CONCLUSIONS: There is a strong relationship between CT quantitative analysis and the COPD candidate gene. Furthermore, the CTGA diplotype was associated with emphysema among the phenotypes of COPD.

Increased Blood Pressure Variability Over a 16-Year Period Is Associated With Left Ventricular Diastolic Dysfunction in a Population-Based Cohort.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is often associated with elevated blood pressure (BP). It is prevalent among hypertensive patients. Additionally, increased BP variability has been linked to LVDD. However, the precise connection between LVDD and BP variability within the general population remains unclear. Thus, this study aimed to evaluate this association in a general population. METHODS: A total of 2,578 participants(1,311 females) with a mean age of 47.8 ±â€…6.7 years who had echocardiographic data from the Korean Genome and Epidemiology study with 16 years of follow-up were analyzed. LVDD was identified through the last echocardiography during the follow-up period. BP variability was assessed using mean, standard deviation (SD), and coefficient of variance (CV). RESULTS: LVDD was detected in 249 individuals. The cohort was divided into an LVDD group and a normal LV diastolic function group. The LVDD group had a higher percentage of females, more advanced age, higher body mass index (BMI), higher BP and BUN levels, lower heart rate, lower hemoglobin, and lower serum creatinine than the normal LV diastolic function group. Remarkably, LVDD was associated with higher BP variability. In the multivariate analysis, LVDD was associated with increased age, female sex, increased BMI, hypertension, and increased BUN. Elevated mean systolic and diastolic BPs, SD of systolic BP, mean pulse pressure (PP), SD of PP, and CV of PP were significantly linked to LVDD even after adjusting for other significant variables in the multivariate analysis. CONCLUSIONS: LVDD was identified in 249 (9.7%) participants. Increased long-term BP variability was significantly associated with LVDD in this population-based cohort.