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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 INTEREST(S) 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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE — The aim of this study was to explore the prevalence and pattern of the metabolic syndrome and its association with hyperinsulinemia in an urban Korean population of 269 men and 505 women. RESEARCH DESIGN AND METHODS — The National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines were used to calculate the sex-specific prevalence of the metabolic syndrome. After excluding individuals taking medication for hypertension, diabetes, or dyslipidemia, we used factor analysis to examine the pattern of the metabolic syndrome in 206 men and 449 women. RESULTS — The prevalence of metabolic syndrome was 16.0% in men and 10.7% in women aged 30-80 years. However, ATP III criteria for central obesity are not optimal for an AsianPacific population; when waist circumference is reduced from 102 to 90 cm in men and 88 to 80 cm in women, the prevalence of the metabolic syndrome increased to 29.0 and 16.8%, respectively. Sex-specific factor analysis showed four factors in men (obesity, glucose intolerance, hypertension, and dyslipidemia) and three in women (obesity-hypertension, glucose intolerance, and obesity-dyslipidemia). Insulin resistance estimated from fasting insulin levels clustered with three of the four factors in men and two of the three factors in women. By ATP III or Asian-Pacific waist circumference criteria, the prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance, which was estimated by a homeostasis model assessment. CONCLUSIONS — The metabolic syndrome is common in an urban Korean population when using Asian-Pacific waist criteria. The prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance. [ABSTRACT FROM AUTHOR]