Jaeseong Jo

Genome-wide association analyses in east Asians identify new susceptibility loci for colorectal cancer

To identify new genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in east Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. We identified four SNPs with association P values of 8.58 × 10−7 to 3.77 × 10−10 in the combined analysis of all east Asian samples. Three of the four were replicated in a study conducted in 26,060 individuals of European descent, with combined P values of 1.22 × 10−10 for rs647161 (5q31.1), 6.64 × 10−9 for rs2423279 (20p12.3) and 3.06 × 10−8 for rs10774214 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both east Asian and European-ancestry populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC.

Low Serum Bilirubin Level as an Independent Predictor of Stroke Incidence A Prospective Study in Korean Men and Women

Background and Purpose— Bilirubin is not only a waste end-product but also an antioxidant. Bilirubin is known to be associated with decrease in cardiovascular risk in men, but its relationship to stroke was not clearly understood. Methods— Serum bilirubin concentrations were measured in 78 724 health examinees (41 054 men, aged 30–89 years) from 1994 to 2001. The subjects with potential hepatobiliary diseases or Gilbert syndrome were excluded from analysis. Stroke incidence outcome was collected from hospital records of admission attributable to stroke from 1994 to 2007. Results— Serum bilirubin measurements were divided into 4 levels: 0 to 10.2, 10.3 to 15.3, 15.4 to 22.1, and 22.2 to 34.2 μmol/L. The number of stroke cases was 1137 in men and 827 in women. In Cox proportional hazard models, participants with a higher level of bilirubin showed lower hazard ratios in men with ischemic stroke after adjustment for multiple confounding factors compared to the lowest level of bilirubin (hazard ratio [HR], 0.72; 95% CI, 0.58–0.90 in level 3; HR, 0.66; 95% CI, 0.49–0.89 in level 4; P for trend=0.016). The risk of all stroke types also decreased as bilirubin levels increased (HR, 0.81; 95% CI, 0.68–0.97 in level 3; HR, 0.74; 95% CI, 0.58–0.94 in level 4; P for trend=0.0071). However, these associations were not seen in hemorrhagic stroke or in women. Conclusions— These findings suggest that serum bilirubin might have some protective function against stroke risk in men.

Smoking and risk of tuberculosis incidence, mortality, and recurrence in South Korean men and women.

The authors explored the association of cigarette smoking with tuberculosis incidence, recurrence, and mortality. A 14-year prospective cohort study (1992-2006) was carried out in 1,294,504 South Koreans. Participants were grouped by smoking history, and the authors assessed tuberculosis incidence, mortality, and recurrence risk for each group. Unadjusted and adjusted Cox proportional hazards models were used to investigate the association between smoking history and the 3 outcomes of interest, adjusting for age and alcohol use. Compared with never smokers, current smokers had increased mortality from tuberculosis among both men (adjusted hazard ratio (HR) = 1.6, 95% confidence interval (CI): 1.3, 2.0) and women (HR = 1.6, 95% CI: 1.0, 2.4). Current male smokers had greater risk of incident tuberculosis than former smokers (HR = 1.4, 95% CI: 1.3, 1.5), and risk among current smokers increased with number of cigarettes smoked daily. In females, cigarette smoking was not associated with incident tuberculosis. There was interaction between smoking and sex for incidence (P = 0.00047). The effect of smoking was generally reduced with adjustment for body mass index. Among men, the highest alcohol consumption category (> or =100 g/day) was associated with risk of incident tuberculosis (HR = 1.5, 95% CI: 1.3, 1.7). This study provides longitudinal evidence that smoking increases risk of incident tuberculosis, mortality from tuberculosis, and tuberculosis recurrence.

Association of physical activity with sarcopenia and sarcopenic obesity in community-dwelling older adults: the Fourth Korea National Health and Nutrition Examination Survey

OBJECTIVE this study examined the association of physical activity with sarcopenia and sarcopenic obesity among the community-dwelling Korean elderly. METHODS subjects consisted of 2,264 aged 65 years or older in the 2008-09 Korea National Health and Nutrition Examination Survey. Sarcopenia was defined as 2 SD below the mean of the appendicular skeletal muscle/weight for healthy young adults. Obesity was defined as waist circumference ≥ 90 cm for men and ≥ 85 cm for women. Levels of physical activity were classified using the metabolic equivalent task method. RESULTS the prevalence of sarcopenia was 12.1% in men and 11.9% in women. Among those with sarcopenia, obesity was prevalent in 68.3% of men and 65.0% of women. Adjusting for all covariates, compared with those with low physical activity, men who engaged in moderate and high activity were 38% and 74%, respectively, less likely to have sarcopenia (Ptrend < 0.001). In women, the relationship between physical activity and sarcopenia was not significant. For sarcopenic obesity, men participating in moderate [odds ratio (OR) = 0.47; 95% confidence interval (CI) 0.26-0.87] and high (OR = 0.27; 95% CI: 0.12-0.60) physical activity, compared with low activity, had significantly lower risk (Ptrend = 0.001). In women, high physical activity was associated with a lower risk of sarcopenic obesity (OR = 0.43; 95% CI: 0.22-0.86). CONCLUSION physical activity is associated with a reduced risk of sarcopenia and sarcopenic obesity in older Korean adults. There were gender differences in the relationship, with stronger associations observed in men than in women.

Serum leptin is associated with metabolic syndrome in obese and nonobese Korean populations

Leptin is mainly secreted from adipose tissue and is known to be associated with cardiovascular diseases. However, there are not many studies on the association between serum leptin and metabolic syndrome. The objective of this study was to determine the association between serum leptin and metabolic syndrome among the Korean adult population. The study population consisted of 3,272 Koreans (men: 1,915, women: 1,357) 30 to 84 years of age who had visited the Health Examination Center. Leptin levels were divided into quintiles and metabolic syndrome was defined by NCEP ATP III. The serum leptin levels increased as the number of components present for metabolic syndrome increased. Controlling for age, smoking, exercise, and LDL cholesterol, subjects with high leptin levels were more likely to have an elevated risk of metabolic syndrome than those with lower levels in both men and women. Subjects in the highest leptin quintile were found to have a higher risk of having metabolic syndrome than those in the lowest quintile (OR = 11.51 for men; OR = 4.65 for women). After further adjustment of the BMI, the risk of metabolic syndrome still increased slightly for men but not for women in increasing leptin categories. This association of leptin levels and metabolic syndrome did not change after stratification into obese and nonobese weight status. Serum leptin is associated with metabolic syndrome in Korean populations independent of body mass index. Thus, the reduction of circulating leptin may confer cardiovascular and metabolic protective effects regardless of weight status.

A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10(-7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10(-165)), ADIPOQ (P = 1.8 × 10(-22)), PEPD (P = 3.6 × 10(-12)), CMIP (P = 2.1 × 10(-10)), ZNF664 (P = 2.3 × 10(-7)) and GPR109A (P = 7.4 × 10(-6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10(-7)). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10(-4)), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10(-4)) and body mass index (BMI)-adjusted waist-hip ratio (P = 9.8 × 10(-3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians

Genome‐wide association studies (GWAS) of colorectal cancer (CRC) have been conducted primarily in European descendants. In a GWAS conducted in East Asians, we first analyzed approximately 1.7 million single‐nucleotide polymorphisms (SNPs) in four studies with 1,773 CRC cases and 2,642 controls. We then selected 66 promising SNPs for replication and genotyped them in three independent studies with 3,612 cases and 3,523 controls. Five SNPs were further evaluated using data from four additional studies including up to 3,290 cases and 4,339 controls. SNP rs7229639 in the SMAD7 gene was found to be associated with CRC risk with an odds ratio (95% confidence interval) associated with the minor allele (A) of 1.22 (1.15–1.29) in the combined analysis of all 11 studies (p = 2.93 × 10−11). SNP rs7229639 is 2,487 bp upstream from rs4939827, a risk variant identified previously in a European‐ancestry GWAS in relation to CRC risk. However, these two SNPs are not correlated in East Asians (r2 = 0.008) nor in Europeans (r2 = 0.146). The CRC association with rs7229639 remained statistically significant after adjusting for rs4939827 as well as three additional CRC risk variants (rs58920878, rs12953717 and rs4464148) reported previously in this region. SNPs rs7229639 and rs4939827 explained approximately 1% of the familial relative risk of CRC in East Asians. This study identifies a new CRC risk variant in the SMAD7 gene, further highlighting the significant role of this gene in the etiology of CRC.

Serum adiponectin as a useful marker for metabolic syndrome in type 2 diabetic patients

Although adiponectin is generally known as a predictor of metabolic syndrome, potential of adiponectin as a predictor for metabolic syndrome in type 2 diabetes is debated. The purpose of this study is to determine the association between adiponectin and metabolic syndrome in patients with type 2 diabetes.

Prediction of Colorectal Cancer Risk Using a Genetic Risk Score: The Korean Cancer Prevention Study-II (KCPS-II)

Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, we developed a prediction model of CRC using genetic risk scores (GRS) and evaluated the effects of conventional risk factors, including family history of CRC, in combination with GRS on the risk of CRC in Koreans. This study included 187 cases (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were calculated with most significantly associated single-nucleotide polymorphism with CRC through a genomewide association study. The area under the curve (AUC) increased by 0.5% to 5.2% when either counted or weighted GRS was added to a prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men and women. Furthermore, the risk of CRC significantly increased for individuals with a family history of CRC in the highest quartile of GRS when compared to subjects without a family history of CRC in the lowest quartile of GRS (counted GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men; OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to 218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest that in Koreans, especially in Korean men, GRS improve the prediction of CRC when considered in conjunction with age and family history of CRC.

Association between Alcohol Intake and Abdominal Obesity among the Korean Population

OBJECTIVES Although abdominal obesity has been reported to be highly related with alcohol intake, the results are still inconclusive. Therefore, this study was conducted to explore the association between alcohol and abdominal obesity among the Korean population. METHODS This study included 8,603 participants (men: 5,195, women: 3,408) aged 30 to 87 who visited the health promotion centers in Seoul for routine health examinations from April, 2006 to June, 2007. Abdominal obesity was defined as WC ≥90 cm for men and ≥85 cm for women in accordance with the Korean Society for the Study of Obesity. For ever drinkers, total alcohol consumption in grams was classified into four groups (group 1, non-drinkers; group 2, 1-10 g of alcohol per day; group 3, 11-20 g of alcohol per day; and group 4, over 20 g of alcohol per day). RESULTS The mean age of the study population was 45.4 yr old (men) and 45.3 yr (women). The average waist circumference was 85.3 cm in men and 75.3 cm in women. A high alcohol intake was associated with high waist circumference in both genders. In multivariate analysis, the group of men and women drinkers consuming >20 g in a day had a large waist circumference compared with men and women non-drinkers. CONCLUSION This study showed that a high alcohol intake was related to high waist circumference. Such association remained independently even after adjustment for smoking, which is strongly related to abdominal obesity.