Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome

Zi-Jiang Chen and colleagues report a genome-wide association analysis for polycystic ovary syndrome (PCOS) in Han Chinese. They identify eight new susceptibility loci for PCOS in this population. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we an...

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Veröffentlicht in:	Nature genetics Jg. 44; H. 9; S. 1020 - 1025
Hauptverfasser:	Shi, Yongyong, Zhao, Han, Shi, Yuhua, Cao, Yunxia, Yang, Dongzi, Li, Zhiqiang, Zhang, Bo, Liang, Xiaoyan, Li, Tao, Chen, Jianhua, Shen, Jiawei, Zhao, Junzhao, You, Li, Gao, Xuan, Zhu, Dongyi, Zhao, Xiaoming, Yan, Ying, Qin, Yingying, Li, Wenjin, Yan, Junhao, Wang, Qingzhong, Zhao, Junli, Geng, Ling, Ma, Jinlong, Zhao, Yueran, He, Guang, Zhang, Aiping, Zou, Shuhua, Yang, Aijun, Liu, Jiayin, Li, Weidong, Li, Baojie, Wan, Chunling, Qin, Ying, Shi, Juanzi, Yang, Jing, Jiang, Hong, Xu, Jin-e, Qi, Xiujuan, Sun, Yun, Zhang, Yajie, Hao, Cuifang, Ju, Xiuqing, Zhao, Dongni, Ren, Chun-e, Li, Xiuqing, Zhang, Wei, Zhang, Yiwen, Zhang, Jiangtao, Wu, Di, Zhang, Changming, He, Lin, Chen, Zi-Jiang
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.09.2012 Nature Publishing Group
Schlagworte:	631/208/205/2138 631/208/2489/144 692/699/2743/1526/1744 Agriculture Animal Genetics and Genomics Apoptosis Asian Continental Ancestry Group - genetics Asian Continental Ancestry Group - statistics & numerical data Biological and medical sciences Biomedicine Cancer Research Case-Control Studies Cell division Cohort Studies Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - ethnology Diabetes Mellitus, Type 2 - genetics Female Female genital diseases Fundamental and applied biological sciences. Psychology Gene Frequency Gene Function Genealogy Genetic aspects Genetic Loci Genetic Predisposition to Disease - ethnology Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study - statistics & numerical data Genomes Genotype Gynecology. Andrology. Obstetrics Health aspects Human Genetics Humans Independent sample Infertility Insulin resistance letter Logistics Medical sciences Meta-Analysis as Topic Metabolic disorders Non tumoral diseases Polycystic ovary syndrome Polycystic Ovary Syndrome - epidemiology Polycystic Ovary Syndrome - ethnology Polycystic Ovary Syndrome - genetics Polymorphism, Single Nucleotide - physiology Proteins Quantitative trait loci R&D Receptors, FSH - genetics Research & development Risk factors Stein-Leventhal syndrome Validation Studies as Topic Women China Ovarian diseases Association Cyst Female sterility Risk Identification Benign neoplasm Polycystic ovary Locus Female genital diseases
ISSN:	1061-4036, 1546-1718, 1546-1718
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Abstract	Zi-Jiang Chen and colleagues report a genome-wide association analysis for polycystic ovary syndrome (PCOS) in Han Chinese. They identify eight new susceptibility loci for PCOS in this population. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10 −8 : 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
AbstractList	Zi-Jiang Chen and colleagues report a genome-wide association analysis for polycystic ovary syndrome (PCOS) in Han Chinese. They identify eight new susceptibility loci for PCOS in this population. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10 −8 : 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 10 super(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS. PCOS also manifests clinically as obesity, infertility, impaired glucose tolerance (IGT), insulin resistance and an increased risk of endometrial cancer, metabolic syndrome, T2D and cardiovascular disease3-5. R, http://www.r-project.org/; LocusZoom, http://csg.sph.umich.edu/locuszoom/; PLINK, http://pngu.mgh.harvard.edu/~purcell/plink/; The International HapMap Project, http://hapmap.ncbi.nlm.nih.gov/; SHEsis, http://analysis.bio-x.cn/myAnalysis.php; MACH, http://www.sph.umich.edu/csg/abecasis/MACH/index.html; IMPUTEv2, https://mathgen.stats.ox.ac.uk/impute/impute_v2.html; The 1000 Genome Project, http://www.1000genomes.org/; Gene Expression Omnibus (GEO), http://www.ncbi.nlm.nih.gov/geo/. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Audience	Academic
Author	Li, Xiuqing Zhang, Yiwen Chen, Zi-Jiang Yang, Aijun Shi, Yongyong Zhao, Yueran Shen, Jiawei Li, Tao He, Lin Zhang, Bo Li, Zhiqiang Cao, Yunxia Zou, Shuhua Hao, Cuifang Zhang, Changming Li, Baojie Zhang, Aiping Liu, Jiayin Wan, Chunling Zhao, Han Yan, Junhao Yan, Ying Li, Weidong Xu, Jin-e He, Guang Yang, Jing Geng, Ling Zhao, Xiaoming Ma, Jinlong Ren, Chun-e Qin, Yingying Qi, Xiujuan Wang, Qingzhong Zhao, Junzhao Gao, Xuan Zhang, Jiangtao Zhu, Dongyi Ju, Xiuqing Qin, Ying Shi, Juanzi Zhang, Wei You, Li Jiang, Hong Chen, Jianhua Zhang, Yajie Liang, Xiaoyan Wu, Di Shi, Yuhua Li, Wenjin Zhao, Junli Sun, Yun Yang, Dongzi Zhao, Dongni
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ContentType	Journal Article
Copyright	Springer Nature America, Inc. 2012 2015 INIST-CNRS COPYRIGHT 2012 Nature Publishing Group Copyright Nature Publishing Group Sep 2012
Copyright_xml	– notice: Springer Nature America, Inc. 2012 – notice: 2015 INIST-CNRS – notice: COPYRIGHT 2012 Nature Publishing Group – notice: Copyright Nature Publishing Group Sep 2012
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Snippet	Zi-Jiang Chen and colleagues report a genome-wide association analysis for polycystic ovary syndrome (PCOS) in Han Chinese. They identify eight new... Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of... PCOS also manifests clinically as obesity, infertility, impaired glucose tolerance (IGT), insulin resistance and an increased risk of endometrial cancer,...
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SubjectTerms	631/208/205/2138 631/208/2489/144 692/699/2743/1526/1744 Agriculture Animal Genetics and Genomics Apoptosis Asian Continental Ancestry Group - genetics Asian Continental Ancestry Group - statistics & numerical data Biological and medical sciences Biomedicine Cancer Research Case-Control Studies Cell division Cohort Studies Diabetes Mellitus, Type 2 - epidemiology Diabetes Mellitus, Type 2 - ethnology Diabetes Mellitus, Type 2 - genetics Female Female genital diseases Fundamental and applied biological sciences. Psychology Gene Frequency Gene Function Genealogy Genetic aspects Genetic Loci Genetic Predisposition to Disease - ethnology Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study - statistics & numerical data Genomes Genotype Gynecology. Andrology. Obstetrics Health aspects Human Genetics Humans Independent sample Infertility Insulin resistance letter Logistics Medical sciences Meta-Analysis as Topic Metabolic disorders Non tumoral diseases Polycystic ovary syndrome Polycystic Ovary Syndrome - epidemiology Polycystic Ovary Syndrome - ethnology Polycystic Ovary Syndrome - genetics Polymorphism, Single Nucleotide - physiology Proteins Quantitative trait loci R&D Receptors, FSH - genetics Research & development Risk factors Stein-Leventhal syndrome Validation Studies as Topic Women
Title	Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome
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