Younjhin Ahn

A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits

To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 × 10−9) and 6q22 (rs12110693, P = 1.6 × 10−9), with the latter ∼400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 × 10−7). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 × 10−12) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 × 10−11), tibia (P = 1.6 × 10−6) and heel (P = 1.9 × 10−10). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 × 10−3, P = 1.4 × 10−7 and P = 6.0 × 10−4, respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.

Prevalence, awareness, treatment, control and risk factors of hypertension in Korea: the Ansan study

Objectives To determine prevalence, awareness, treatment, and control of hypertension, and its risk factors in an urban Korean population. Design and setting A cross-sectional survey in Ansan-city, Korea. Subjects and methods Population-based samples of people aged 18–92 years in Ansan-city, Korea, were selected, yielding 2278 men and 1948 women, and their blood pressures were measured using a highly standardized protocol. Hypertension was defined as a systolic BP ⩾ 140 mmHg or diastolic BP ⩾ 90 mmHg or reported treatment with antihypertensive medications, and subclassified according to 1999 WHO-ISH guidelines. Isolated systolic hypertension (ISH) defined as a systolic BP ⩾140 mmHg and diastolic BP < 90 mmHg was also examined. Data were stratified by age and sex. Results The overall prevalence of hypertension in this study was 33.7%. Among these, 64.9% had Grade 1 hypertension, 22.5% Grade 2, and 12.5% Grade 3. Age-specific prevalence of hypertension increased progressively with age, from 14.19% in 18 to 24 year-olds to 71.39% in those 75 years or older. Hypertension prevalence was significantly higher in men (41.5%) than in women (24.5%) (P < 0.001). Isolated systolic hypertension had significantly lower prevalence (4.33%) within the population, although in the elderly aged 55 years or more it rose by 11.13%. Overall, 24.6% of hypertensive individuals were aware that they had high blood pressure, as much as 78.6% were being treated with antihypertensive medications, and 24.3% were under control. Hypertension awareness as well as treatment and control rates varied by sex, with women higher in all three rates. Multivariate analysis revealed that age, body mass index and abdomen circumference were significantly associated with prevalence of hypertension both in men and women. Conclusions Hypertension is highly prevalent in Korea. Despite the high rate of treatment, the rates of awareness and control are relatively low, suggesting the nationwide demand for preventing and controlling high blood pressure in Korea in order to avert an epidemic of cardiovascular disease.

Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans

BACKGROUNDnAssociations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors.nnnMETHODSnWe genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database.nnnRESULTSnWith a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P=0.025, OR=1.47, 95% CI=1.05-2.06; P=0.023, OR=1.53, 95% CI=1.06-2.22) and adults (P=0.018, OR=1.10, 95% CI=1.02-1.19; P=0.001, OR=1.16, 95% CI=1.06-1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P=0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P=0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found.nnnCONCLUSIONSnFTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.

Relative validities of 3-day food records and the food frequency questionnaire

The food frequency questionnaire (FFQ) has been used as an important dietary assessment tool in epidemiologic studies, but the usefulness of the FFQ has been debated in recent years. This study was performed to evaluate the relative validities of 3-day food records and the semi-quantitative FFQ. A total of 124 subjects finished 3-day food records (FRs) during each of the four seasons, as well as the FFQ from December 2002 to May 2004. The FFQ was a food based semi-quantitative FFQ including 103 items. Three-day FRs from each season and a randomly selected season were compared with the remaining 9-day FRs. The remaining 9-day FRs, as a reference measurement, were also compared with the FFQ. Pearsons correlation coefficients between the 3-day FRs and the 9-day FRs were between 0.14 and 0.56. Pearsons correlation coefficients between the FFQ and the 9-day FRs ranged between 0.07 and 0.41. Average proportions of classification into the same quartiles, adjacent quartiles, and distant quartiles between the 3-day FRs and the 9-day FRs were 35.8%, 40.5%, and 5.2%, respectively. On average, the proportions of classification into the same quartiles, adjacent quartiles, and distant quartiles between the FFQ and the 9-day FRs were 31.1%, 39.4%, and 6.9%, respectively. Three-day FRs showed higher correlations and higher agreement proportions of quartile classification with the 9-day FRs than did the FFQ, but both relative validities of 3-day FRs and the FFQ appear to be acceptable as dietary assessment tools. Further studies for validating food intake by reliable biomarkers are necessary.

A Prospective Study Investigating the Association Between Environmental Tobacco Smoke Exposure and the Incidence of Type 2 Diabetes in Never Smokers

PURPOSEnWe studied a cohort of individuals to assess whether intensity of environmental tobacco smoke (ETS) exposure is associated with the incidence of type 2 diabetes.nnnMETHODSnStudy subjects were selected from an ongoing population-based cohort of Korea Genome and Epidemiology Study. Participants of the baseline study 10,038 persons within the age range of 40 to 69 years old. Among 4,442 never smokers without prevalent diabetes, 465 type 2 diabetes cases were identified through biennial active follow-ups for a 6-year period. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) after adjustment for covariates.nnnRESULTSnThe risk of type 2 diabetes was higher in subjects exposed to ETS compared with the nonexposure group (HR = 1.41, 95% CI: 1.1-1.70). Daily exposure to ETS at home increased the risk of type 2 diabetes when compared with the risk level of nonexposure (HR = 1.46, 95% CI: 1.16-1.83). Over 4 hours exposure to ETS at home and in the workplace was associated with increased the risk of type 2 diabetes (HR = 1.96, 95% CI: 1.21-3.19).nnnCONCLUSIONSnOur study suggests that ETS exposure is a significant risk factor for the development of type 2 diabetes with dose-response relationship.

Dietary pattern classifications with nutrient intake and health-risk factors in Korean men.

OBJECTIVEnThis study was performed to identify dietary patterns in Korean men and to determine the associations among dietary patterns, nutrient intake, and health-risk factors.nnnMETHODSnUsing baseline data from the Korean Health and Genome Study, dietary patterns were identified using factor analysis of data from a validated food-frequency questionnaire, and associations between these dietary patterns and health-risk factors were analyzed.nnnRESULTSnThree dietary patterns were identified: 1) the animal-food pattern (greater intake of meats, fish, and dairy products), 2) the rice-vegetable pattern (greater intake of rice, tofu, kimchi, soybean paste, vegetables, and seaweed), and 3) the noodle-bread pattern (greater intake of instant noodles, Chinese noodles, and bread). The animal-food pattern (preferred by younger people with higher income and education levels) had a positive correlation with obesity and hypercholesterolemia, whereas the rice-vegetable pattern (preferred by older people with lower income and educational levels) was positively associated with hypertension. The noodle-bread pattern (also preferred by younger people with higher income and education levels) had a positive association with abdominal obesity and hypercholesterolemia.nnnCONCLUSIONnThis study identifies three unique dietary patterns in Korean men, which are independently associated with certain health-risk factors. The rice-vegetable dietary pattern, modified for a low sodium intake, might be a healthy dietary pattern for Korean men.

Rice-eating pattern and the risk of metabolic syndrome especially waist circumference in Korean Genome and Epidemiology Study (KoGES)

BackgroundMetabolic syndrome poses a serious health threat in Asian countries. Rice is a staple food in Korea, and carbohydrate intake is associated with the risk of MetS. We hypothesized that various rice-eating patterns in a carbohydrate-based diet would have different effects on the risk of MetS.MethodsParticipants were 26,006 subjects enrolled in the Korean Genome and Epidemiology Study between 2004 and 2006. They were classified into four dietary patterns - white rice, rice with beans, rice with multi-grains, and mixed based on their food frequency questionnaire responses. We compared metabolic risk traits according to the rice-eating patterns.ResultsNutrients consumption and the presence of MetS risk factors differed according to rice-eating patterns. In men odds ratio(OR) for central obesity was slightly elevated in mixed group(1.18). In women, the risk for central obesity and abnormal fasting glucose were lower in the rice with beans group (adjusted OR =0.79, 0.83 respectively) and central obesity in rice with multi-grains(adjusted OR=0.91) than the white rice group. In postmenopausal women, ORs for central obesity (0.78) and abnormal fasting glucose (0.75) in the rice with beans group and ORs for central obesity (0.83), abnormal HDL-cholesterol (0.87) and MetS(0.85) in the rice with multi-grains group was lower than those in white rice group. In premenopausal women, the risk for central obesity (OR=0.77) was reduced in the rice with beans group.ConclusionThe risk for MetS was lower in the rice with beans and rice with multi-grains groups compared with the white rice group, particularly in postmenopausal women.

Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: results from the Korean Genome and Epidemiology Study

Aims/hypothesisTo examine the association between soybean products and risk of type 2 diabetes, we measured four isoflavone biological markers—genistein, daidzein, glycitein and equol—in a nested case–control study.MethodsThe study population was composed of 693 cases (316 women and 377 men) and 698 matched controls (317 women and 381 men) within the Korean Genome and Epidemiology Study. The concentrations of isoflavone biomarkers were measured using HPLC-MS/MS on plasma samples that were collected at baseline. A stratified analysis was undertaken to examine the association between plasma isoflavone concentrations and risk of type 2 diabetes according to sex and equol production. Logistic regression models were used to compute ORs and 95% CIs adjusted for confounders.ResultsIn women, compared with the lowest quartile of plasma concentration of genistein, the highest quartile exhibited a significantly decreased risk of diabetes (OR 0.58, 95% CI 0.35, 0.95). When stratified by equol-producing status in women, the OR for diabetes in the highest vs the lowest quartile of genistein concentration was 0.31 (95% CI 0.16, 0.60) in equol producers, but genistein concentration was not associated with risk of diabetes in equol non-producers (p for interactionu2009=u20090.013). In men, isoflavone concentrations were not associated with risk of diabetes, regardless of equol-producing status.Conclusions/interpretationHigh plasma concentrations of genistein were associated with a decreased risk of type 2 diabetes in women. This inverse association was prominent in equol-producing participants. These results suggest a beneficial effect of a high intake of soybean products on risk of type 2 diabetes in women.

Recapitulation of the association of the Val66Met polymorphism of BDNF gene with BMI in Koreans.

Recent evidence suggests that brain‐derived neurotrophic factor (BDNF) regulates food intake and the control of body weight. A common polymorphism in human BDNF, Val66Met (single‐nucleotide polymorphism database (dbSNP) no. rs6265), impairs intracellular trafficking, resulting in the reduced secretion of BDNF. Several European studies have indicated that Val66Met is associated with BMI. In this study, we examined the association of the Val66Met polymorphism with BMI in Koreans (n = 20,270) from three independent epidemiological cohorts. All three studies observed a consistent association of this polymorphism with BMI, and their combined analysis demonstrated a robust correlation (β = −0.17 ± 0.03 and P = 5.6 × 10−8). We also examined the effect of smoking on the link between Val66Met and BMI. The association of Val66Met with BMI was statistically significant only in the smoking group, reflecting a possible interaction between smoking and the BDNF polymorphism for BMI. Thus, we have confirmed BDNF as a genetic risk factor for BMI in an Asian population and hypothesize that the Val66Met mutation influences individual differences in BMI. In addition, smoking might interact with BDNF Val66Met to modulate BMI.

Association between physical activity and menopausal symptoms in perimenopausal women.

BackgroundPhysical activity may be an effective way of preventing or attenuating menopause-related symptoms, and it has been shown to improve quality of life in menopausal women. However, there have been some inconsistencies regarding between exercise and menopausal symptoms, and study investigating this association has been scarce in Korea. In this study, the association between physical activity and menopausal symptoms in perimenopausal women in Korea was assessed.MethodsThis cross-sectional observational study was conducted between November 2012 and March 2013. In total, 2,204 healthy women aged 44–56 years were recruited from a healthcare center at the Kangbuk Samsung hospitals for investigating women’s attitudes towards menopause. To investigate the influence of physical activity on perimenopause-associated symptoms, 631 perimenopausal women were selected for this study. Their physical activity levels were assessed using the International Physical Activity Questionnaire (IPAQ) short form. The Menopause-specific Quality of Life (MENQOL) questionnaire was used to assess menopause-related symptoms.ResultsThe study participants were, on average, 48.5u2009±u20092.7xa0years old and had a mean body mass index of 22.8u2009±u20093.1xa0kg/m2. The total MENQOL score and the psychosocial and physical subscores exhibited U-shaped trends in relation to the level of physical activity. Multiple linear regression analysis adjusted for confounding variables showed that perimenopausal women who performed moderate physical activity reported significantly lower psychosocial (βu2009=u2009-0.413, Pu2009=u20090.012) and physical symptoms (βu2009=u2009-0.445, Pu2009=u20090.002) than women who performed low physical activity. By contrast, a high level of physical activity did not influence the MENQOL total score and subscores relative to the low activity group. In addition, no associations were observed between physical activity and the vasomotor and sexual symptoms in any group.ConclusionsModerate level of physical activity was associated with reduced psychosocial and physical menopause symptoms in perimenopausal Korean women. Although these findings must be confirmed by prospective longitudinal studies, they suggest that physical activity may improve the symptoms of menopause, thereby increasing quality of life.