Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3
Zi-Jiang Chen and Yongyong Shi report a genome-wide association study for polycystic ovary syndrome, a common metabolic and endocrine disorder in women. They identified three susceptibility loci associated with this condition. Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women....
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| Vydáno v: | Nature genetics Ročník 43; číslo 1; s. 55 - 59 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
New York
Nature Publishing Group US
01.01.2011
Nature Publishing Group |
| Témata: | |
| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
| On-line přístup: | Získat plný text |
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| Abstract | Zi-Jiang Chen and Yongyong Shi report a genome-wide association study for polycystic ovary syndrome, a common metabolic and endocrine disorder in women. They identified three susceptibility loci associated with this condition.
Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined
P
-value by meta-analysis
P
meta
= 7.55 × 10
−21
, odds ratio (OR) 0.71); 2p21 (rs13429458,
P
meta
= 1.73 × 10
−23
, OR 0.67); and 9q33.3 (rs2479106,
P
meta
= 8.12 × 10
−19
, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. |
|---|---|
| AbstractList | Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P^sub meta^ = 7.55 × 10^sup -21^, odds ratio (OR) 0.71); 2p21 (rs13429458, P^sub meta^ = 1.73 × 10^sup -23^, OR 0.67); and 9q33.3 (rs2479106, P^sub meta^ = 8.12 × 10^sup -19^, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. [PUBLICATION ABSTRACT] Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P sub(meta) = 7.55 10 super(-21), odds ratio (OR) 0.71); 2p21 (rs13429458, P sub(meta) = 1.73 10 super(-23), OR 0.67); and 9q33.3 (rs2479106, P sub(meta) = 8.12 10 super(-19), OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. Zi-Jiang Chen and Yongyong Shi report a genome-wide association study for polycystic ovary syndrome, a common metabolic and endocrine disorder in women. They identified three susceptibility loci associated with this condition. Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P -value by meta-analysis P meta = 7.55 × 10 −21 , odds ratio (OR) 0.71); 2p21 (rs13429458, P meta = 1.73 × 10 −23 , OR 0.67); and 9q33.3 (rs2479106, P meta = 8.12 × 10 −19 , OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rsl 3405728; combined P-value by meta-analysis [P.sub.meta] = 7.55 x [10.sup.-21], odds ratio (OR) 0.71); 2p21 (rs13429458, [P.sub.meta] = 1.73 x [10.sup.-23], OR 0.67); and 9q33.3 (rs2479106, [P.sub.meta] = 8.12 x [10.sup.-19], OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended. |
| Audience | Academic |
| Author | Zhao, Xiaoming Ma, Jinlong Ren, Chun-e Qin, Yingying Chen, Zi-Jiang Li, Yiran Yang, Aijun Shi, Yongyong Zhao, Junzhao Gao, Xuan Zhao, Yueran Bian, Yuehong He, Lin Zhang, Bo Chen, Shiling Li, Zhiqiang Zhu, Dongyi Hao, Cuifang Zhang, Wei You, Li Jiang, Hong Liu, Jiayin Zhang, Yajie Liang, Xiaoyan Zhao, Han Yan, Junhao Sun, Xiuqin Li, Yuan Shi, Yuhua Zhao, Junli Xu, Jin-e Geng, Ling Sun, Yingpu Zhao, Dongni |
| Author_xml | – sequence: 1 givenname: Zi-Jiang surname: Chen fullname: Chen, Zi-Jiang email: zjchen59@yahoo.com organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 2 givenname: Han surname: Zhao fullname: Zhao, Han organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 3 givenname: Lin surname: He fullname: He, Lin organization: Institutes of Biomedical Sciences, Fudan University, Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences – sequence: 4 givenname: Yuhua surname: Shi fullname: Shi, Yuhua organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 5 givenname: Yingying surname: Qin fullname: Qin, Yingying organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 6 givenname: Yongyong surname: Shi fullname: Shi, Yongyong email: shiyongyong@gmail.com organization: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University – sequence: 7 givenname: Zhiqiang surname: Li fullname: Li, Zhiqiang organization: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University – sequence: 8 givenname: Li surname: You fullname: You, Li organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 9 givenname: Junli surname: Zhao fullname: Zhao, Junli organization: Affiliated Hospital of Ningxia Medical University – sequence: 10 givenname: Jiayin surname: Liu fullname: Liu, Jiayin organization: The First Affiliated Hospital with Nanjing Medical University – sequence: 11 givenname: Xiaoyan surname: Liang fullname: Liang, Xiaoyan organization: The Sixth Affiliated Hospital of Sun Yat-sen University – sequence: 12 givenname: Xiaoming surname: Zhao fullname: Zhao, Xiaoming organization: Renji Hospital Affiliated to Shanghai Jiaotong University – sequence: 13 givenname: Junzhao surname: Zhao fullname: Zhao, Junzhao organization: The First Affiliated Hospital of Wenzhou Medical College – sequence: 14 givenname: Yingpu surname: Sun fullname: Sun, Yingpu organization: The First Affiliated Hospital of Zhengzhou University – sequence: 15 givenname: Bo surname: Zhang fullname: Zhang, Bo organization: Maternal and Child Health Hospital in Guangxi – sequence: 16 givenname: Hong surname: Jiang fullname: Jiang, Hong organization: 105th Hospital of People's Liberation Army – sequence: 17 givenname: Dongni surname: Zhao fullname: Zhao, Dongni organization: Shengjing Hospital of China Medical University – sequence: 18 givenname: Yuehong surname: Bian fullname: Bian, Yuehong organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 19 givenname: Xuan surname: Gao fullname: Gao, Xuan organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 20 givenname: Ling surname: Geng fullname: Geng, Ling organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 21 givenname: Yiran surname: Li fullname: Li, Yiran organization: Qingdao Women & Children Medical Healthcare Center, Affiliated Hospital of Weifang Medical College – sequence: 22 givenname: Dongyi surname: Zhu fullname: Zhu, Dongyi organization: Linyi People's Hospital – sequence: 23 givenname: Xiuqin surname: Sun fullname: Sun, Xiuqin organization: Shandong Jingning First People's Hospital – sequence: 24 givenname: Jin-e surname: Xu fullname: Xu, Jin-e organization: The Affiliated Hospital of Medical College Qingdao University – sequence: 25 givenname: Cuifang surname: Hao fullname: Hao, Cuifang organization: Yantai Yuhuangding Hospital – sequence: 26 givenname: Chun-e surname: Ren fullname: Ren, Chun-e organization: Affiliated Hospital of Weifang Medical College – sequence: 27 givenname: Yajie surname: Zhang fullname: Zhang, Yajie organization: Jinan Health Institute of Maternity and Infant – sequence: 28 givenname: Shiling surname: Chen fullname: Chen, Shiling organization: Nanfang Hospital – sequence: 29 givenname: Wei surname: Zhang fullname: Zhang, Wei organization: Obstetrics & Gynecology Hospital of Fudan University – sequence: 30 givenname: Aijun surname: Yang fullname: Yang, Aijun organization: Affiliated Hospital of Jining Medical College – sequence: 31 givenname: Junhao surname: Yan fullname: Yan, Junhao organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 32 givenname: Yuan surname: Li fullname: Li, Yuan organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 33 givenname: Jinlong surname: Ma fullname: Ma, Jinlong organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China – sequence: 34 givenname: Yueran surname: Zhao fullname: Zhao, Yueran organization: Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21151128$$D View this record in MEDLINE/PubMed |
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Reprod.20092420142022 ZegginiEMeta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetesNat. Genet.200840638645 LatronicoACLinsTSBritoVNArnholdIJMendoncaBBThe effect of distinct activating mutations of the luteinizing hormone receptor gene on the pituitary-gonadal axis in both sexesClin. Endocrinol.200053609613 JC Barrett (BFng732_CR37) 2005; 21 JM Korn (BFng732_CR32) 2008; 40 Y Wang (BFng732_CR11) 2006; 86 AC Latronico (BFng732_CR18) 1998; 12 S Sudo (BFng732_CR10) 2002; 8 M Huang (BFng732_CR17) 2006; 17 C Hu (BFng732_CR26) 2009; 4 YY Shi (BFng732_CR35) 2005; 15 S Xu (BFng732_CR15) 2009; 85 AC Latronico (BFng732_CR20) 2000; 53 J Du (BFng732_CR23) 2010; 100 ZJ Chen (BFng732_CR12) 2004; 39 Y Shi (BFng732_CR9) 2007; 28 CS Carlson (BFng732_CR14) 2004; 429 B Kulshreshtha (BFng732_CR8) 2008; 24 G Thomas (BFng732_CR33) 2004; 25 E Kandaraki (BFng732_CR5) 2009; 53 N Drieschner (BFng732_CR24) 2006; 16 O Valkenburg (BFng732_CR21) 2009; 24 K Del Villar (BFng732_CR27) 2004; 101 E Carmina (BFng732_CR4) 2009; 12 L Petukhova (BFng732_CR36) 2010; 466 R Saxena (BFng732_CR38) 2007; 316 JJ Espinós-Gómez (BFng732_CR7) 2009; 25 J Radziuk (BFng732_CR31) 2000; 85 MO Goodarzi (BFng732_CR2) 2006; 20 DA Ehrmann (BFng732_CR3) 1999; 22 AL Price (BFng732_CR16) 2006; 38 BFng732_CR1 M Olszanecka-Glinianowicz (BFng732_CR28) 2007; 133 Y Shi (BFng732_CR30) 2008; 90 G Villuendas (BFng732_CR13) 2002; 87 N Mantel (BFng732_CR39) 1959; 22 P Yi (BFng732_CR34) 2009; 29 S Wild (BFng732_CR6) 2000; 3 SPA Toledo (BFng732_CR19) 1996; 81 D Ferriman (BFng732_CR29) 1961; 21 Y Tong (BFng732_CR22) 2001; 33 E Zeggini (BFng732_CR25) 2008; 40 19177453 - Prenat Diagn. 2009 Mar;29(3):217-22 19944404 - Am J Hum Genet. 2009 Dec;85(6):762-74 19811236 - Climacteric. 2009;12 Suppl 1:22-5 16772151 - Best Pract Res Clin Endocrinol Metab. 2006 Jun;20(2):193-205 15498182 - Zhonghua Fu Chan Ke Za Zhi. 2004 Sep;39(9):582-5 11134088 - J Clin Endocrinol Metab. 2000 Dec;85(12):4426-33 20399696 - Mol Genet Metab. 2010 Jul;100(3):292-5 18372903 - Nat Genet. 2008 May;40(5):638-45 11889177 - J Clin Endocrinol Metab. 2002 Mar;87(3):1134-41 20596022 - Nature. 2010 Jul 1;466(7302):113-7 10333916 - Diabetes Care. 1999 Jan;22(1):141-6 19031221 - Gynecol Endocrinol. 2008 Nov;24(11):637-43 19466215 - Arq Bras Endocrinol Metabol. 2009 Mar;53(2):227-37 8923827 - J Clin Endocrinol Metab. 1996 Nov;81(11):3850-4 11844363 - Hum Fertil (Camb). 2000;3(2):101-105 9514160 - Mol Endocrinol. 1998 Mar;12(3):442-50 15007167 - Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4210-5 12356937 - Mol Hum Reprod. 2002 Oct;8(10):893-9 17889857 - Fertil Steril. 2008 Oct;90(4):1139-43 17224231 - Eur J Obstet Gynecol Reprod Biol. 2007 Aug;133(2):197-202 11106922 - Clin Endocrinol (Oxf). 2000 Nov;53(5):609-13 13655060 - J Natl Cancer Inst. 1959 Apr;22(4):719-48 11383926 - Horm Metab Res. 2001 Apr;33(4):221-6 16525715 - Int J Mol Med. 2006 Apr;17(4):599-604 15740637 - Cell Res. 2005 Feb;15(2):97-8 19862325 - PLoS One. 2009 Oct 28;4(10 ):e7643 18063948 - Neuro Endocrinol Lett. 2007 Dec;28(6):807-10 14711538 - Fertil Steril. 2004 Jan;81(1):19-25 19347711 - Gynecol Endocrinol. 2009 Mar;25(3):199-204 16764871 - Fertil Steril. 2006 Jul;86(1):223-6 17463246 - Science. 2007 Jun 1;316(5829):1331-6 17123335 - Thyroid. 2006 Nov;16(11):1091-6 18776909 - Nat Genet. 2008 Oct;40(10):1253-60 16862161 - Nat Genet. 2006 Aug;38(8):904-9 15297300 - Bioinformatics. 2005 Jan 15;21(2):263-5 15164069 - Nature. 2004 May 27;429(6990):446-52 13892577 - J Clin Endocrinol Metab. 1961 Nov;21:1440-7 19403562 - Hum Reprod. 2009 Aug;24(8):2014-22 15188256 - Electrophoresis. 2004 Jun;25(10-11):1668-77 |
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| Snippet | Zi-Jiang Chen and Yongyong Shi report a genome-wide association study for polycystic ovary syndrome, a common metabolic and endocrine disorder in women. They... Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of... |
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| SubjectTerms | 631/208/205/2138 631/208/727/2000 692/699/2743/1526/1744 Agriculture Animal Genetics and Genomics Asian Continental Ancestry Group Biomedical and Life Sciences Biomedicine Body mass index Cancer Research Chromosome Mapping Chromosomes Chromosomes, Human, Pair 2 - genetics Chromosomes, Human, Pair 9 - genetics Confidence intervals Disease susceptibility Female Gene Function Genetic aspects Genetic Predisposition to Disease Genetics Genome, Human - genetics Genome-Wide Association Study Genotype Human Genetics Humans Hypothyroidism Insulin resistance letter Meta-Analysis as Topic Metabolic disorders Methods Odds Ratio Physiological aspects Polycystic ovary syndrome Polycystic Ovary Syndrome - genetics Principal components analysis Risk factors Single nucleotide polymorphisms Stein-Leventhal syndrome Studies |
| Title | Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3 |
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