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Background/aims: Although increased serum anti-Müllerian hormone (AMH) level has been suggested to be a surrogate marker of polycystic ovarian morphology (PCOM), its association with polycystic ovary syndrome (PCOS) is controversial, and its diagnostic value has not been determined. We aimed to observe the relationship between the AMH level and PCOS phenotypes and to determine the optimal cutoff value of AMH for the diagnosis of PCOS in young Korean women., Methods: We recruited 207 women with PCOS (120 with PCOM and 87 without PCOM) and 220 regular cycling women with normoandrogenemia (100 with PCOM and 120 without PCOM). Subjects underwent testing at a single outpatient visit. Serum AMH level was measured., Results: Women with PCOS had higher serum AMH levels than did regular cycling women with normoandrogenemia ( p < 0.05). Women with PCOM had higher serum AMH levels than women without PCOM, regardless of PCOS status ( p < 0.05). The optimal AMH cutoff value for the diagnosis of PCOS was 10.0 ng/mL (71% sensitivity, 93% specificity). Serum AMH was an independent determinant of total testosterone after adjustment for age, body mass index, and the number of menses/year (β = 0.31, p < 0.01). An association between AMH and hyperandrogenism was only observed in women with PCOS, and it was independent of the presence of PCOM., Conclusion: The serum AMH level can be useful for the diagnosis of PCOS at any age less than 40 years, and the optimal cutoff value for the diagnosis of PCOS identified in this study of young Korean women was 10.0 ng/mL.

Purpose: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS., Materials and Methods: We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs)., Results: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p<0.05)., Conclusion: The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in young Korean women with PCOS, and women with NFG and a high TG/HDL-C ratio had a higher prevalence of IGT. Therefore, Korean women with PCOS with a TG/HDL-C ratio >2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG., Competing Interests: The authors have no financial conflicts of interest.

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., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

Study Question: Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)?, Summary Answer: We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women., What Is Known Already: PCOS is a highly complex disorder with significant contributions from both genetic and environmental factors. Previous genome-wide association studies (GWAS) in the Han Chinese population identified several risk loci for PCOS. However, GWAS studies on PCOS remain very few. The aim of this study was to identify novel markers of susceptibility to PCOS through GWAS., Study Design, Size, Duration: A two-stage GWAS was conducted. The initial discovery set for GWAS consisted of 976 PCOS cases and 946 controls. The second stage (replication study) included 249 PCOS cases and 778 controls., Participants/materials, Setting, Methods: Patients were diagnosed according to the Rotterdam criteria. Genomic DNAs were genotyped using the HumanOmni1-Quad v1 array. In the replication stage, the 21 most promising signals selected from the discovery stage were tested for their association with PCOS., Main Results and the Role of Chance: One novel locus with genome-wide significance and seven moderately associated loci for PCOS were identified. The strongest association was on chromosome 8q24.2 (rs10505648, OR = 0.52, P = 5.46 × 10(-8)), and other association signals were located at 4q35.2, 16p13.3, 4p12, 3q26.33, 9q21.32, 11p13 and 1p22 (P = 5.72 × 10(-6)-6.43 × 10(-5)). The strongest signal was located upstream of KHDRBS3, which is associated with telomerase activity, and could drive PCOS and related phenotypes., Limitations, Reasons for Caution: The limitation of our study is the modest sample size used in the replication cohort. The limited sample size may contribute to a lack of statistical power to detect an association or show a trend in severity., Wider Implications of the Findings: Our findings provide new insight into the genetics and biological pathways of PCOS and could contribute to the early diagnosis and prevention of metabolic and reproductive morbidities., Study Funding/competing Interests: This work was supported in part by the grant from the Korea Centers for Disease Control and Prevention (2009-E00591-00). The work was also supported by the Ewha Global Top5 Grant 2013 of Ewha Womans University. None of the authors has any conflict of interest to declare., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To determine the features of polycystic ovary syndrome (PCOS) that are implicated in the associated reproductive and metabolic morbidities., Design: Cross-sectional case-control study., Setting: Academic medical setting., Patient(s): A total of 1,062 women with PCOS and 1,887 women without PCOS., Intervention(s): None., Main Outcome Measure(s): Physical examination including hirsutism scoring, biochemical and hormone measurements, ovarian ultrasound, and a 75-g oral glucose tolerance test to measure glucose and insulin levels., Result(s): A factor analysis identified four dominant factors in women with PCOS. These factors were interpreted as follows: [1] metabolic and hyperandrogenemia factor, [2] oligomenorrhea and hyperandrogenemia factor, [3] blood pressure factor, and [4] ovarian morphology factor. In women with PCOS, hyperandrogenemia was a significant predictor of metabolic syndrome after adjusting for age, body mass index, and insulin resistance in the regression analysis., Conclusion(s): A factor analysis identified multiple factors that are responsible for the abnormalities associated with PCOS. Hyperandrogenemia was a common underlying feature of the metabolic and reproductive abnormalities in women with PCOS but not in women without PCOS., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Although menstrual irregularity is associated with insulin resistance and hyperandrogenism, the relationship between the severity of menstrual infrequency and clinical phenotypes in young women with oligomenorrhoea (OM) is unclear. We evaluated whether a longer menstrual cycle length is associated with less favourable metabolic features., Design/patients/measurements: A total of 1174 young women (aged 19-39 years) with a menstrual cycle length over 40 days and 1430 women with regular menstrual cycles participated voluntarily. Metabolic parameters, insulin sensitivity index (ISI) and testosterone were measured. Oligomenorrhoeic women were divided into three groups: (i) polycystic ovary syndrome (PCOS) by National Institute of Health criteria, (ii) severe OM (menstrual cycle length >60 days), and (iii) mild OM (menstrual cycle length 40-60 days)., Results: In normal-weight women (BMI < 23 kg/m(2)), the degrees of insulin resistance and hyperandrogenaemia are the highest in PCOS and higher in severe OM compared with mild OM. In overweight or obese women, PCOS was more insulin resistant and hyperandrogenaemic, but there was no difference between severe and mild OM. After excluding PCOS, women with severe OM showed a twofold increased risk of metabolic syndrome compared with regular cycling women (odds ratio 2·4, 95% confidence interval 1·1-5·6). By linear regression analysis, a longer menstrual cycle length was associated with ISI after adjustment for age, BMI, metabolic risk factors and testosterone., Conclusions: Women with a menstrual cycle length over 60 days should be more closely monitored for the metabolic syndrome than women with a menstrual cycle length of 40-60 days, even if they have no PCOS., (© 2013 John Wiley & Sons Ltd.)

Objective: Visceral fat accumulation is more strongly related to insulin resistance than to excess total adiposity. The visceral adiposity index (VAI) has recently been suggested as an indicator of the visceral adiposity measured by magnetic resonance imaging. To evaluate whether the VAI could replace visceral computed tomography (CT) scanning and predict insulin resistance in young women with polycystic ovary syndrome (PCOS) was presented., Design and Methods: One hundred and eighty Korean women aged 16-41 years who were diagnosed with PCOS using the Rotterdam criteria were included. The VAI was derived from a formula using body mass index, waist circumference, triglycerides, and high-density lipoprotein cholesterol. Visceral adiposity was defined as a visceral fat area (VFA) measuring > 100 cm(2) by CT scanning. Insulin sensitivity was evaluated by insulin-mediated glucose utilization (M value), which was obtained using a euglycemic hyperinsulinemic clamp., Results: The VAI positively correlated with VFA, the visceral-to-subcutaneous fat ratio, and systolic and diastolic blood pressure, and negatively correlated with the M value. In a linear regression analysis, the VAI was an independent determinant of the insulin sensitivity after controlling for age, systolic blood pressure, fasting glucose, fasting insulin, and testosterone levels. In a logistic regression analysis, the VAI odds ratio was 3.5 (95% CI 1.2-9.8) for predicting visceral adiposity after controlling for the various metabolic parameters and testosterone., Conclusion: The VAI can replace visceral CT scanning as a marker for visceral adiposity, and it predicts insulin resistance in young women with PCOS., (Copyright © 2013 The Obesity Society.)

Background/aims: Many women with polycystic ovary syndrome (PCOS) exhibit insulin resistance. Adipose tissue plays an important role in insulin resistance, and adipokines including tumor necrosis factor (TNF)-α and adiponectin are altered in PCOS. Insulin-like growth factor binding protein-3 (IGFBP-3), alone or in conjunction with other adipokines, is also associated with insulin resistance. We evaluated the effects of TNF-α, adiponectin, and IGFBP-3 on insulin sensitivity and the relationships among these proteins in women with PCOS., Methods: We recruited 40 women with PCOS and 40 age- and body mass index (BMI)-matched regular cycling women (controls). The women were divided into obese (BMI ≥ 25 kg/m(2)) and nonobese (BMI < 25 kg/m(2)) groups. Anthropometric measurements were performed, and serum levels of TNF-α, adiponectin, and IGFBP-3 were determined. Insulin sensitivity was estimated using the metabolic clearance rate (MCR) of glucose calculated from the oral glucose tolerance test., Results: Serum levels of TNF-α and IGFBP-3 did not differ between the PCOS and control groups, but adiponectin levels in the PCOS group were lower than those in control women in the nonobese group (p < 0.05). TNF-α, adiponectin, and IGFBP-3 levels were not correlated with each other in women with PCOS, but a significant positive correlation was observed between adiponectin levels and MCR (p < 0.05). Multiple regression analysis revealed that adiponectin levels were significantly associated with insulin sensitivity (p < 0.05) in women with PCOS., Conclusions: IGFBP-3 and TNF-α levels were not associated with insulin sensitivity, but adiponectin levels were related to insulin sensitivity in women with PCOS.

Purpose: Approximately 50% to 70% of women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and obesity is known to worsen insulin resistance. Many metabolic consequences of PCOS are similar to those of obesity; therefore, defining the cause of insulin resistance in women can be difficult. Our objective was to clarify the factors contributing to insulin resistance in PCOS., Materials and Methods: We consecutively recruited 144 women with PCOS [age: 26±5 yr, body mass index, body mass index (BMI): 24.4±4.0 kg/m2] and 145 controls (age: 25±5 yr, BMI: 23.0±3.6 kg/m2), and divided them into overweight/obese (ow/ob, BMI≥23 kg/m2) and lean (BMI<23 kg/m2) groups. Anthropometric measures and a 75-g oral glucose tolerance test were performed, and insulin sensitivity index (ISI) was calculated as an index of insulin sensitivity. Factors predictive of ISI were determined using regression analysis., Results: ISI was significantly lower in both lean and ow/ob women with PCOS compared to BMI-matched controls (p<0.05). Increasing BMI by 1 kg/m2 decreased ISI by 0.169 in PCOS patients (p<0.05) and by 0.238 in controls (p<0.05); there was no significant difference between these groups. In lean PCOS patients and lean controls, BMI had no effect on ISI. Multiple regression analysis revealed that PCOS status (β=-0.423, p<0.001) and BMI (β=-0.375, p<0.001) were significantly associated with ISI., Conclusion: Insulin resistance is an intrinsic defect of PCOS, and a high BMI could exacerbate insulin resistance in all women, irrespective of whether they have PCOS.

The International Diabetes Federation consensus proposed an ethnically specific criteria of waist circumference (WC) for central obesity, but, the nationwide definition is still debated in Korea. For the detection of the optimal WC cutoff value, the nonadipose components of the metabolic syndrome (MS) were defined by modification of revised 2003 Rotterdam consensus as having two or more risk factors such as hypertension, hyperglycemia, and dyslipidemia without consideration of abdominal obesity. By using receiver-operating characteristic (ROC) curve analysis, cutoff points of WC and visceral fat area (VFA) for prediction of MS were 80 cm and 53.1 cm(2). WC cutoff points corresponding to VFA >53.1 and 100 cm(2) were 73.3 and 77.8 cm. The sensitivity and specificity of currently used value of WC 88 cm were 41.9 and 91.5%, suggesting that it could be too high in Korean population. Central obesity defined as WC >80 cm was significantly associated with nonadipose components of MS after adjustment for age, BMI, cholesterol, triglycerides, fasting insulin, and free testosterone levels. Central obesity with WC of >80 cm predicted the presence of nonadipose MS (odds ratio 16.6; 95% confidence interval (CI) 6.5-42.6). It was also significant (odds ratio 14.7; 95% CI 3.4-64.3) when we applied the WC value of 70 cm instead of 80 cm. In conclusion, WC of 80 and 70 cm could be appropriate cutoff points to identify the MS and visceral adiposity in Korean women with polycystic ovary syndrome (PCOS), respectively. Therefore, PCOS women with a WC over 70 cm should be closely monitored for the development of MS.

Background/aims: Serum levels of highly sensitive C-reactive protein (hsCRP), a vascular inflammatory marker, may predict the development of cardiovascular disease (CVD) and type 2 diabetes. Women with polycystic ovary syndrome (PCOS) are at greater risk for type 2 diabetes and CVD. The aim of this study was to compare hsCRP levels between normal weight women with PCOS and controls with a normal menstrual cycle and to determine the factors associated with serum hsCRP levels., Methods: Thirty-nine lean PCOS patients and 24 healthy, regular cycling women were enrolled in this study. We performed anthropometric measurements, fat computed tomography (CT), and blood sampling to determine blood chemistry and levels of hsCRP, gonadotropins, testosterone, and sex-hormone binding globulin. We also conducted 75-g oral glucose-tolerance test and euglycemic hyperinsulinemic clamp to assess insulin sensitivity., Results: Serum hsCRP concentrations were higher in women with PCOS than in women with regular mensturation. However, this difference was no longer significant after adjusting for body mass index (BMI). hsCRP levels were correlated with waist circumference (r=0.46, p<0.01), BMI (r=0.46, p<0.01), visceral fat area (r=0.45, p<0.01), and systolic (r=0.42, p<0.05) and diastolic blood pressure (r=0.39, p<0.05). hsCRP also tended to be negatively associated with insulin-mediated glucose uptake (IMGU) (r=-0.31, p=0.07). A multiple regression analysis revealed that BMI (beta=0.29, p<0.05), systolic blood pressure (beta=0.39, p<0.01), and IMGU (beta=-0.31, p<0.05) predicted serum hsCRP levels in women with PCOS., Conclusions: PCOS by itself does not seem to be associated with increased hsCRP levels, whereas known CVD risk factors affect serum hsCRP levels in PCOS.

Insulin resistance and hyperinsulinemia play important roles in the pathogenesis of polycystic ovary syndrome (PCOS). In addition, some women with PCOS have been shown to have insulin secretory defects and can be predicted to be at an increased risk for glucose intolerance. We performed the present study to determine the prevalence and risk factors for glucose intolerance in Korean women with PCOS. We consecutively recruited 194 women with PCOS diagnosed by American Society for Reproductive Medicine/European Society of Human Reproduction and Embryology (ASRM/ESHRE) criteria. Anthropometric measures, 75 g oral glucose tolerance test (OGTT), and measurement of insulin sensitivity (insulin mediated glucose uptake; IMGU) using euglycemic hyperinsulinemic clamp technique were performed. In women with PCOS, the prevalence of impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) was 17.0% and type 2 diabetes 1.0%, and in lean women with PCOS, the prevalence of IGT and/or IFG was 5.9%. The prevalence of glucose intolerance was 28-fold higher in women with PCOS, and 9.8-fold higher in lean women with PCOS compared to age-matched Korean women. Women with glucose intolerance had higher BMI, waist circumference, free testosterone, fasting insulin, 2-h post-load insulin, total cholesterol, LDL cholesterol, triglyceride and lower sex hormone binding globulin and IMGU than women with normal glucose tolerance (NGT) (P < 0.05). IMGU was the most powerful predictor for glucose intolerance after adjustment for age, BMI, waist circumference, and hyperandrogenemia. The 2-h OGTT was the best screening measure for glucose intolerance and diagnosis of diabetes in women with PCOS. Young Korean women with PCOS have high prevalence for glucose intolerance and type 2 diabetes, and insulin resistance is the most important factor associated with glucose intolerance.

Over 50% of women with polycystic ovary syndrome (PCOS) have been reported to have varying degree of insulin resistance and it may contribute to hyperandrogenism. The aim of the study is to identify whether the insulin resistance is present in non-obese Korean women with PCOS and whether the phenotype is different according to insulin sensitivity. Seventy-three non-obese (BMI<23 kg/m(2)) women with PCOS and 34 age and BMI comparable control women with regular menstrual cycles were examined. Standard 75 g OGTT was performed to determine the status of glucose tolerance. Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp technique. The fasting plasma glucose (p<0.01) and post-glucose load plasma insulin (p<0.01) of women with PCOS were higher than those of controls. Glucose disposal rate (M-value) was lower in women with PCOS compared to controls (p<0.05). Insulin resistant (IR) and insulin sensitive (IS) PCOS were divided by the M-value of 25-percentile (5.5mg/kg min) in controls. Between IR and IS groups, DHEAS (p<0.01), post-glucose load plasma insulin (p<0.05) showed differences after the adjustment for BMI. Our non-obese women with PCOS showed significant insulin resistance compared to their age and BMI comparable control subjects and their insulin resistance may contribute to hyperandrogenism especially via adrenal androgen overproduction.

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and consequent hyperinsulinemia. Insulin resistance also plays an important role in the metabolic syndrome (MS). We conducted a cross-sectional study to determine the prevalence of the MS in young Korean women with PCOS and whether it is associated insulin resistance. One hundred and seventeen young women with PCOS (age: 26+/-5, 16-39 years) were evaluated for the frequency of MS according to the modified Adult Treatment Panel III. Total testosterone (T), free T, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured, and insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp technique. The prevalence of MS in women with PCOS was 14.5%, nearly 3.5-fold higher than in age-matched women in Korean urban population (4.3%) [J.-Y. Oh, Y.-A. Sung, Y.S. Hong, E. Barrett-Conner, Prevalence and factor analysis of metabolic syndrome in an urban Korean population, Diabetes Care 27 (2004) 2027-2032]. The most frequently occurring component of MS was low HDL cholesterol (45%), and the least frequent was high fasting serum glucose level (0.9%). PCOS women with MS had significantly higher free T, and lower SHBG compared with those without MS. And women with MS showed significantly lower M-value and higher fasting/post-glucose load insulin levels. M-value was still significantly lower in women with MS even after the adjustment for BMI. MS is frequent in young Korean women with PCOS and it reflects more severe insulin resistance. These results suggest the importance of early and regular screening of metabolic disturbance in even young women with PCOS.

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]