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Study Question: Is a genetic risk score (GRS) associated with polycystic ovary syndrome (PCOS) and its related clinical features?Summary Answer: The GRS calculated by genome-wide association studies (GWASs) was significantly associated with PCOS status and its related clinical features.What Is Known Already: PCOS is a heterogeneous disorder and is characterized by oligomenorrhea, hyperandrogenism and polycystic ovary morphology. Although recent GWASs have identified multiple genes associated with PCOS, a comprehensive genetic risk study of these loci with PCOS and related traits (e.g. free testosterone, menstruation number/year and ovarian morphology) has not been performed.Study Design, Size, Duration: This study was designed as a cross-sectional case-control study. We recruited 862 women with PCOS and 860 controls. Women with PCOS were divided into four subgroups: (1) oligomenorrhea + hyperandrogenism + polycystic ovary, (2) oligomenorrhea + hyperandrogenism, (3) oligomenorrhea + polycystic ovary and (4) hyperandrogenism + polycystic ovary.Participants/materials, Settings, Methods: Genomic DNA was genotyped for the PCOS susceptibility loci using the HumanOmni1-Quad v1 array. Venous blood was drawn in the early follicular phase to measure baseline metabolic and hormonal parameters. A GRS was calculated by summing the number of risk alleles from 11 single-nucleotide polymorphisms (SNPs) that were identified in previous GWASs on PCOS. A weighted GRS (wGRS) was calculated by multiplying the number of risk alleles for each SNP by its estimated effect (beta) obtained from the association analysis.Main Results and the Role Of Chance: The GRS was higher in women with PCOS than in controls (8.8 versus 8.2, P < 0.01) and was significantly associated with PCOS after adjusting for age and BMI. An analysis of GRS quartiles (Q1 = 3-5, Q2 = 6-8, Q3 = 9-11, Q4 = 12-15) revealed that the subjects in the highest quartile showed a remarkable increased risk of PCOS compared with those in the lowest quartile (odds ratio = 6.28, P < 0.001). Free testosterone level, menstruation number per year, ovarian volume and ovarian follicle numbers were significantly associated with the GRS (in all cases, P < 0.01). The wGRS yielded similar results.Limitations, Reasons For Caution: We used 11 loci for the calculation of GRS, but a higher number of PCOS risk alleles was reported in previous studies. Therefore, further studies should assess the value of GRS including the additional SNPs related to PCOS. Although a GRS of ≥12 was significantly associated with PCOS, the GRS showed a poor predictive value; therefore, the use of genetic information based on current GWAS data only may present problems.Wider Implications Of the Findings: The GRS could be used to identify asymptomatic individuals among people at risk and stratify them into accurate risk categories for the purpose of individualizing treatment approaches, which could potentially improve health outcomes.Study Funding/competing Interests: None of the authors have any conflicts of interest to declare. No funding was obtained for the study. [ABSTRACT FROM AUTHOR]

Background: The fat mass and obesity-associated (FTO) gene is associated with obesity and type 2 diabetes mellitus. Obesity and insulin resistance are also common features of polycystic ovary syndrome (PCOS). Therefore, the FTO gene might be a candidate gene for PCOS susceptibility. The aim of the present study was to evaluate the effects of FTO gene variants on PCOS susceptibility and metabolic and reproductive hormonal parameters., Methods: We recruited 432 women with PCOS (24±5 years) and 927 healthy women with regular menstrual cycles (27±5 years) and performed a case-control association study. We genotyped the single nucleotide polymorphisms rs1421085, rs17817449, and rs8050136 in the FTO gene and collected metabolic and hormonal measurements., Results: Logistic regression revealed that the G/G genotype (rs1421085, 1.6%), the C/C genotype (rs17817449, 1.6%), and the A/A genotype (rs8050136, 1.6%) were strongly associated with an increased risk of PCOS (odds ratio, 2.551 to 2.559; all P<0.05). The strengths of these associations were attenuated after adjusting for age and BMI. The women with these genotypes were more obese and exhibited higher free androgen indices (P<0.05) and higher free testosterone levels (P=0.053 to 0.063) compared to the other genotypes. However the significant differences disappeared after adjusting for body mass index (BMI). When we analyzed the women with PCOS and the control groups separately, there were no significant differences in the metabolic and reproductive hormonal parameters according to the FTO gene variants., Conclusion: The rs1421085, rs17817449, and rs8050136 variants of the FTO gene were associated with PCOS susceptibility and hyperandrogenemia in young Korean women. These associations may be mediated through an effect of BMI.

Background: Although diabetes is a well-known risk factor for death, its impact on cancer death is not clearly understood. Furthermore, it remains controversial whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality. We investigated the impact of diabetes or glucose tolerance categories on all cause and cause-specific mortality., Methods: Mortality analysis was conducted in three population-based cohort studies of 3,801 participants, divided according to fasting plasma glucose (FPG) (normal; stage 1 IFG [5.6≤FPG<6.1 mmol/L]; stage 2 IFG [6.1≤FPG<7.0 mmol/L]; diabetes mellitus [DM]-FPG); or 2-hour glucose after 75 g glucose loading (2hPG) (normal; IGT; DM-2hPG), or a combination of FPG and 2hPG criteria., Results: During a median follow-up of 11.0 years, 474 subjects died from all causes. Hazard ratios (HRs) for all cause death were higher in those with diabetes as defined by either FPG or 2hPG criteria than their normal counterparts (HR, 2.2, 95% confidence interval [CI], 1.6 to 2.9 for DM-FPG; HR, 2.0, 95% CI, 1.5 to 2.7 for DM-2hPG). Similarly, diabetes defined by either FPG or 2hPG was associated with cancer death (HR, 2.9, 95% CI, 1.7 to 5.0; and HR, 2.1, 95% CI, 1.2 to 3.9, respectively). Although neither IFG nor IGT conferred higher risk for death, when combining stage 2 IFG and/or IGT, the risk of all cause death was higher than in subjects with normal glucose regulation (HR, 1.3; 95% CI, 1.0 to 1.6)., Conclusion: Diabetes is associated with higher risk of death from all causes and cancer. In subjects without diabetes, stage 2 IFG and/or IGT confers increased risk for mortality.

There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.