Multiple susceptibility loci at chromosome 11q23.3 are associated with plasma triglyceride in East Asians.

Genetic studies of plasma TG levels have identified associations with multiple candidate loci on chromosome11q23.3, which harbors a number of genes, including BUD13, ZNF259, and APOA5-A4-C3-A1. This study aimed to examine whether these multiple candidate genes on the 11q23.3 regions exert independent effects on TG levels or whether their effects are confounded by linkage disequilibrium (LD). We performed a genome-wide association study and consequent fine-mapping analyses on TG levels in two Korean population-based cohorts: the Korea Association Resource study (n = 8,223) and the Healthy Twin study (n = 1,735). A total of 301 loci reached genome-wide significance level in pooled analysis, including 10 SNPs with weak LD (r(2) < 0.06) clustered on 11q23.3: ApoA5 (rs651821, rs2075291); ZNF259 (rs964184, rs603446); BUD13 (rs11216126); Apoa4 (rs7396851); SIK3 (rs12292858); PCSK7 (rs199890178); PAFAH1B2 (rs12420127), and SIDT2 (rs2269399). When the inter-dependence between alleles was examined using conditional models, five loci on BUD13, ZNF259, and ApoA5 showed possible independent associations. A haplotype analysis using five SNPs revealed both hyper- and hypotriglyceridemic haplotypes, which are relatively common in Koreans (haplotype frequency 0.08-0.22). Our findings suggest the presence of multiple functional loci on 11q23.3, which might exert their effects on plasma TG level independently or through complex interactions between functional loci.

Modifying effects of resting heart rate on the association of binge drinking with all-cause and cardiovascular mortality in older Korean men: the Kangwha Cohort Study.

BACKGROUND: Although binge drinking and high resting heart rate independently affect cardiovascular and all-cause mortality risk, the combined effect of these two risk factors and their interaction has rarely been studied. This study examined the association between binge drinking and cardiovascular and all-cause mortality and evaluated the potential modifying effect on this association of resting heart rate in Korean men. METHODS: Men aged 55 years or older in 1985 (n = 2600) were followed for cardiovascular and all-cause mortality for 20.8 years, until 2005. We estimated hazard ratios (HRs) for cardiovascular and all-cause mortality by binge drinking and resting heart rate using the Cox proportional hazard model. RESULTS: Heavy binge drinkers (≥12 drinks on one occasion) with elevated resting heart rate (≥80 bpm) had a HR of 2.25 (95% confidence interval [CI], 1.47-3.45) for death from cardiovascular disease and 1.37 (95% CI, 0.87-2.14) for all-cause mortality compared to the reference group (non-drinking and resting heart rate 61-79 bpm). The HRs of dying from cardiovascular disease increased linearly from 1.36 to 1.52, 1.71, and 2.25 among individuals with resting heart rate greater than or equal to 80 bpm within the four alcohol consumption categories (non-drinking, non-binge, moderate binge, and heavy binge), respectively. CONCLUSIONS: Our findings suggest that, among older Korean men, heavy binge drinkers with an elevated resting heart rate are at high risk for cardiovascular and all-cause mortality.

The Healthy Twin Study, Korea updates: resources for omics and genome epidemiology studies.

The Healthy Twin Study, Korea (HT) is an ongoing multi-center cohort study that was initiated in 2005, based on a nation-wide twin and family database. Since its inception, the HT has recruited 815 pairs of adult twins and a total of 3,690 individual twins and their families as of July 2012. Here we summarize updates since the previous report in 2006. Besides the increase in size, the HT has been enriched in several aspects: a biobank was constructed for ongoing and future omics studies; and genome-wide single nucleotide polymorphism markers (Affymetrix GeneChip version 6.0, 1 M probes) have been analyzed for 2,200 individuals, which enabled gene identification studies for measured phenotypes. In addition, longitudinal study protocols were established through the HT and a second wave survey was finished in 2010 with >70% follow-up rate. The parallel genome research projects were recently launched, which would expedite multi-omics studies maximizing the twin potentials such as metagenomics and epigenetics studies, and endow us with resources for recruiting more participants. We submit this report to share updates and research opportunities from the HT.

Resources and pilot results for establishing a Mongolian Twin Register.

Despite the need to provide evidence-based health policy, most developing countries suffer from a lack of resources for sound epidemiologic evidence. Most twin registers have been established in developed countries and there are relatively fewer twin registers in developing countries. Considering the immense potential of twin research, it will be worthwhile to attempt to establish a new twin register in Mongolia, where biomedical studies are still scarce. Our objectives were to initiate the process of establishing a nation-wide twin register in Mongolia, based on a nation-wide, population-based database. With the approval and support of the Ministry of Population Development and Social Welfare of Mongolia, we were able to access an initial list of 411 twin pairs who live in the district of Ulaanbaatar, the capital city of Mongolia. By developing a questionnaire to estimate zygosity, we conducted a pilot survey. Those who registered consisted of 822 individuals or 411 twin pairs (same sex: male - 178; female - 157; different sex - 76), two sets of triplets (same sex: female - 2). The age of twins ranged from 1 to 81 (mean age 7.3 ± 11.3), and 52.4% were males. The first twin survey in Mongolia not only resulted in interim data for the Mongolian Twin Register, but has the potential for establishing a larger register by using the national database. It has been proven possible to establish a twin register for research purposes in Mongolia.

Life satisfaction and mortality in elderly people: the Kangwha Cohort Study.

BACKGROUND: As well as biomedical risk factors, psychological factors have been reported to be related to mortality rate. The purpose of this study was to examine the relationship between life satisfaction and mortality in elderly people through an 11.8-year follow-up study of a prospective cohort. METHODS: Among 3,600 participants of the Kangwha Cohort Study who survived in 1994, 1,939 respondents of the Life Satisfaction Index (LSI)-A questionnaire were included (men, 821; women, 1118). The mortality risk for the period up to December 2005 was measured using the Cox Proportional Hazard Model. RESULTS: When the relationship between LSI and mortality was evaluated in men, the unsatisfied group with lower LSI scores showed a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.11-1.83) than the satisfied group with higher LSI scores. In women, the unsatisfied group showed a significantly higher risk of all-cause mortality (HR, 1.51; 95% CI, 1.18-1.92) and cardiovascular mortality (HR, 2.23; 95% CI, 1.30-3.85) than the satisfied group. CONCLUSION: We found that elderly people with a lower LSI score, regardless of gender, were at risk of increased mortality from all causes, and low LSI score was also associated with cardiovascular mortality.

Combined effects of cognitive impairment and hypertension on total mortality in elderly people: the Kangwha Cohort study.

BACKGROUND: Previous studies have shown links between cognitive impairment and hypertension as well as mortality. However, combined effects of these two conditions on mortality have not been fully explored. OBJECTIVE: To assess the combined effect of cognitive impairment and hypertension on all-cause mortality among the elderly people. METHODS: We followed a cohort of 2,496 residents in Kangwha County, ranging in age from 64 to 101 years as of March 1994, for all-cause mortality for 11.8 years up to December 31, 2005. We calculated hazard ratios (HR) for all-cause mortality by cognitive status and blood pressure using the Cox proportional hazards model after having controlled for confounding factors. RESULTS: 1,189 people (47.6%) died during the 11.8 years of follow-up. The HR associated with severe cognitive impairment increased from 2.15 (95% CI: 1.30, 3.54) for prehypertension over 2.68 (95% CI: 1.60, 4.48) for stage 1 hypertension to 3.60 (95% CI: 1.99, 6.49) for stage 2 hypertension in women. A mortality risk of 3.67 (95% CI: 2.05, 6.57) was observed among men who had both mild cognitive impairment and stage 2 hypertension. CONCLUSION: Individuals with coexisting cognitive impairment and hypertension are at an increased risk of all-cause mortality compared with those with cognitive impairment or hypertension alone.

Heritability and linkage study on heart rates in a Mongolian population.

Elevated heart rate has been proposed as an independent risk factor for cardiovascular diseases, but their interrelationships are not well understood. In this study, we performed a genome-wide linkage scan in 1,026 individuals (mean age 30.6 years, 54.5% women) from 73 extended families of Mongolia and determined quantitative trait loci that influence heart rate. The DNA samples were genotyped using deCODE 1,039 microsatellite markers for 3 cM density genome-wide linkage scan. Correlation analysis was carried out to evaluate the correlation of the covariates and the heart rate. T-tests of the heart rate were also performed on sex, smoking and alcohol intake. Consequently, this model was used in a nonparametric genome-wide linkage analysis using variance component model to create a multipoint logarithm of odds (LOD) score and a corresponding P value. In the adjusted model, the heritability of heart rate was estimated as 0.32 (P<.0001) and a maximum multipoint LOD score of 2.03 was observed in 77 cM region at chromosome 18. The second largest LOD score of 1.52 was seen on chromosome 5 at 216 cM. Genes located on the specified locations in chromosomes 5 and 18 may be involved in the regulation of heart rate.

Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia.

The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

Population based study of the association between binge drinking and mortality from cancer of oropharynx and esophagus in Korean men: the Kangwha cohort study.

We assessed the association between frequency of heavy binge drinking and mortality from oropharynx and esophagus cancer after controlling for the total volume of alcohol intake among Korean men. The cohort comprised 2,677 male residents in Kangwha County, aged 55 or older in March 1985, for their upper digestive tract cancer mortality for 20.8 years up to December 31, 2005. For daily binge drinkers versus non-drinkers, the hazard ratios (95% Cls) for mortality were 4.82 (1.36, 17.1) and 6.75 (1.45, 31.4) for oropharyngeal and esophageal cancers, respectively. Even after adjusting for the volume of alcohol intake, we found the hazard ratios for frequency of binge drinking and mortality of oropharyngeal or esophageal cancer to not change appreciably: the hazard ratios were 4.90 (1.00, 27.0) and 7.17 (1.02, 50.6), respectively. For esophageal cancer, there was a strong dose-response relationship. The frequency of heavy binge drinking and not just the volume of alcohol intake may increase the risk of mortality from upper digestive tract cancer, particularly esophageal cancer in Korean men. These findings need to be confirmed in further studies with a larger sample size.

Gender-specific combined effects of smoking and hypertension on cardiovascular disease mortality in elderly Koreans: THe Kangwha Cohort Study.

OBJECTIVE: We examined gender-specific combined effects of smoking and hypertension on risk of mortality from cardiovascular disease in elderly Korean men and women. STUDY DESIGN: This study followed a cohort of 6097 residents (2593 men, 3504 women) in the general population of Kangwha County, aged ≥55 years in March 1985 and examined their cause-specific mortality for 20.8 years, up to December 31, 2005. All participants were followed up more than once after the 1985 survey. MAIN OUTCOME MEASURES: We calculated hazard ratios for mortality for the combined sets of smoking habits and blood pressure levels using the Cox proportional-hazard model. The set of non-smokers with normal blood pressure served as a reference group. RESULTS: During the 20.8 years of follow-up, 759 people died from cardiovascular disease. The risk of mortality from cardiovascular disease and stroke according to smoking or hypertension was not different between men and women. However, the risk among smokers combined with hypertension was higher in men than in women; the multivariable-adjusted hazard ratios (95% CI) for mortality from cardiovascular disease and stroke were 4.52 (1.67-12.21) and 6.37 (1.57-25.85) in men and 2.11 (1.37-3.24) and 2.41 (1.44-4.01) in women, respectively. CONCLUSIONS: The magnitude of the joint effects of smoking and hypertension on cardiovascular disease and stroke mortality was different between men and women. This study suggests that combining quitting smoking with lowering blood pressure could contribute to preventing cardiovascular disease and stroke, especially in men.