Lee Hyejin, Oh Jee-Young, Sung Yeon-Ah, Chung Hyewon, Kim Hyung-Lae, Kim Gwang Sub, Cho Yoon Shin, Kim Jin Taek
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
Hum Reprod. 2015 Mar;30(3):723-31. doi: 10.1093/humrep/deu352. Epub 2015 Jan 8.
Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)?
We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women.
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.
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.
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.
是否存在多囊卵巢综合征（PCOS）易感性的新型遗传标记物？
我们在韩国女性中确定了8号染色体q24.2上的一个新型易感位点以及几个与PCOS中度相关的位点。
PCOS是一种高度复杂的疾病，遗传和环境因素都有重要影响。先前针对中国汉族人群的全基因组关联研究（GWAS）确定了PCOS的几个风险位点。然而，关于PCOS的GWAS研究仍然很少。本研究的目的是通过GWAS确定PCOS易感性的新型标记物。
研究设计、规模、持续时间：进行了两阶段GWAS。GWAS的初始发现集包括976例PCOS病例和946例对照。第二阶段（重复研究）包括249例PCOS病例和778例对照。
参与者/材料、研究环境、方法：根据鹿特丹标准对患者进行诊断。使用HumanOmni1-Quad v1阵列对基因组DNA进行基因分型。在重复阶段，对从发现阶段选出的21个最有希望的信号进行与PCOS的关联测试。
确定了一个具有全基因组意义的新型位点和七个与PCOS中度相关的位点。最强关联位于8号染色体q24.2（rs10505648，OR = 0.52，P = 5.46×10⁻⁸），其他关联信号位于4q35.2、16p13.3、4p12、3q26.33、9q21.32、11p13和1p22（P = 5.72×10⁻⁶ - 6.43×10⁻⁵）。最强信号位于与端粒酶活性相关的KHDRBS3上游，可能导致PCOS及相关表型。
局限性、谨慎原因：我们研究的局限性在于重复队列中使用的样本量适中。样本量有限可能导致缺乏检测关联或显示严重程度趋势的统计效力。
我们的发现为PCOS的遗传学和生物学途径提供了新见解，并可能有助于代谢和生殖疾病的早期诊断和预防。
研究资金/利益冲突：本研究部分得到了韩国疾病控制与预防中心的资助（2009 - E00591 - 00）。该研究还得到了梨花女子大学2013年梨花全球Top5资助。作者均无利益冲突需要声明。
