Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes. METHODS: We used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed. RESULTS: The pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05). CONCLUSIONS: By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS.

Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE) Cohorts.

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m(2)). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10(-6)), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10(-7), Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

Association between extraversion personality and abnormal glucose regulation in young Korean women.

Depression and psychological distress are known to be associated with diabetes development as well as the disease progression including glycemic control and chronic complication, but relationship of personality with diabetes is controversial. We examined whether personality trait and the presence of abnormal glucose regulation (AGR; diabetes and pre-diabetes) are associated in young women. A total of 1,617 young women aged 19-39 years without previously diagnosed diabetes were participated voluntarily. Personality trait was assessed by self-reported questionnaire using the five-factor model (neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) consisting of five-point scale ranging from 'strongly disagreeable' to 'strongly agreeable.' Glucose tolerance status was assessed by standard 75-g oral glucose tolerance test. One hundred and eleven women were newly diagnosed with AGR (6.9 %). Among five factors, only extraversion trait was significantly associated with AGR. Multiple linear regression analysis showed significant negative association between extraversion trait and 2-h post-load glucose after adjustment for age, BMI, systolic blood pressure, triglycerides, HDL cholesterol and family history of diabetes (ß = -0.16, P = 0.026). Multiple logistic regression showed extraversion trait having a significant association with the presence of AGR after adjustment for the same covariates (OR 0.97, 95 % CI 0.95-0.99, P = 0.011). The frequency of AGR was significantly increased according to the decrease in extraversion score (P for trend with exact test = 0.047). In conclusion, extraversion may be an important personality trait having a beneficial effect on decreasing the risk of AGR.

Personality traits and body mass index in a Korean population.

BACKGROUND: Overweight and obesity is a serious problem worldwide related to cardiovascular and other diseases. Personality traits are associated with the abnormal body mass indices (BMIs) indicative of overweight and obesity. However, the links between personality traits and BMI have been little studied in Korea. METHODS: We evaluated the association between personality traits and BMI in men and women using the rural Ansung and urban Ansan cohort from the Korean Genome Epidemiology Study, and the Kangbuk Samsung Hospital Cohort Study datasets. A shorter version of the original Revised Neuroticism-Extroversion-Openness Personality Inventory (NEO-PI-R) was used to measure the five-factor model of personality (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness). RESULTS: Data from a total of 1,495 men (mean age 60.0 ± 9.8 years; mean BMI 24.3 ± 3.0 kg/m2) and 2,547 women (mean age 47.0 ± 15.5 years; mean BMI 22.8 ± 3.4 kg/m2) were included in the analysis. Compared with the normal weight groups, overweight and obese men scored higher on openness to experience and lower on conscientiousness. Overweight and obese women scored lower on neuroticism and openness to experience and higher on agreeableness. Extraversion was positively associated with BMI in men (ß=0.032, P<0.05). BMI and waist circumference were significantly increased in individuals who were less dutiful. In women, neuroticism was inversely associated with BMI (ß=-0.026, P<0.05). Openness to experience was negatively, and agreeableness was positively, associated with BMI (openness to experience: ß=-0.072, agreeableness ß=0.068) and waist circumference (openness to experience: ß=-0.202, agreeableness: ß=0.227) (P<0.05). CONCLUSION: Personality traits were associated with underweight, overweight, and obesity in men and women. Increased understanding of the underlying factors contributing to this association will aid in the prevention and treatment of abnormal BMI.

Association between blood lipid levels and personality traits in young Korean women.

Abnormal lipid levels are important etiological factors associated with the development of atherosclerosis and with increased cardiovascular morbidity and mortality. Lipid levels are also influenced by lifestyle and behavioral factors, which suggests that personality traits might be related to abnormal lipid profiles. Studies on personality traits and lipid levels are relatively scarce in Korea. Therefore, the objective of this study was to examine the association between lipid levels and personality traits in young Korean women. A total of 1,701 young Korean women [mean age  = 24.9±4.6 years (range 17-39)] who volunteered for personality trait evaluation were recruited for this study. Lipid levels, including total cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride, were measured in all subjects after an overnight fast, and a low density lipoprotein (LDL) cholesterol level was calculated. The study population was divided into abnormal and normal lipid level groups according to the clinical criteria. Personality traits were measured using the Revised NEO Personality Inventory for the Five-Factor Model of personality. High neuroticism was associated with low HDL cholesterol levels. Low extraversion and openness were associated with high levels of triglyceride. At the facet level, the association between personality and lipid levels were generally consistent. Angry hostility, self-consciousness, vulnerability to stress, activity, and straightforwardness were associated with HDL cholesterol levels. Activity, positive emotion, aesthetics, actions, and deliberation were associated with triglyceride. When applying clinical criteria, conscientiousness was less likely to have abnormal total cholesterol levels. Our results showed that the women with the low HDL cholesterol levels are like to be more neurotic and the hyperglycemic women are prone to lower extraversion and openness in Korea. Understanding the associations between blood lipid levels and personality traits may have a beneficial effect for the managing of dyslipidemia.

Sleep disorder and cardiovascular risk factors among patients with type 2 diabetes mellitus.

BACKGROUND/AIMS: Sleep disorder (SD) is associated with an increased risk of cardiovascular disease and is more prevalent among individuals with type 2 diabetes mellitus. These health problems not only frequently coexist but also exacerbate each other. We conducted a cross-sectional study to estimate the prevalence of SD among diabetic patients and to investigate the relationship between SD and cardiovascular risk among these patients. METHODS: We recruited 784 patients with type 2 diabetes and conducted a self-administered questionnaire. We assessed sleep quality using the Pittsburgh Sleep Quality Index and the risk of obstructive sleep apnea (OSA) using the Berlin Questionnaire. Additional information included blood pressure and metabolic profiles. RESULTS: Of the 784 diabetic patients, 301 (38.4%) patients had poor sleep quality, and 124 (15.8%) were at high risk for OSA. Patients at increased risk for OSA were more obese; they also had higher blood pressure, fasting plasma insulin levels, insulin resistance assessed by homeostasis model assessment (HOMA-IR), and serum triglycerides levels (p < 0.05). The frequency of risk for OSA was higher among obese patients compared with non-obese patients (34.8% vs. 9.4%, p < 0.05). Logistic regression analysis revealed that male sex and bone mass index were independent predictors of risk for OSA. CONCLUSIONS: SD was prevalent among type 2 diabetic patients, and OSA could aggravate their risk for cardiovascular disease. Clinical treatment of these patients should include evaluation and intervention for SD.

Long menstrual cycle is associated with type 2 diabetes mellitus in korean women.

BACKGROUND: Long menstrual cycle is a risk factor for developing type 2 diabetes and cardiovascular disease in women. We aimed to evaluate the association between existing type 2 diabetes and oligomenorrhea before diagnosis of diabetes, and to observe the differences in this association among obese and non-obese Korean women. METHODS: Patients with type 2 diabetes (n=118) and without any clinical evidence of abnormal glucose regulation (n=258) who attended the outpatient clinic of a university hospital and were over age 30. Patients self-reporting a menstrual cycle over 40 days during their 20s were defined as oligomenorrhea before diagnosis of diabetes. Obesity was defined as having a body mass index (BMI) over 25 kg/m(2). RESULTS: The frequency of oligomenorrhea before diagnosis of diabetes was almost two-fold higher in women with type 2 diabetes than in the control group (16.1% vs. 8.5%, P=0.03). Oligomenorrhea was associated with type 2 diabetes after adjusting for age, BMI, systolic blood pressure, triglycerides, and high density lipoprotein cholesterol (odds ratio, 3.89; 95% confidence interval, 1.37 to 11.04). Among women with oligomenorrhea before diagnosis of diabetes, the frequency of type 2 diabetes was significantly higher in obese subjects than in their non-obese counterparts (90.9% vs. 30.0%, P=0.03). CONCLUSION: Having a long menstrual cycle could be a risk factor for the development of type 2 diabetes, especially in obese women.