| Title | Association of 8q22.3 locus in Chinese Han with idiopathic premature ovarian failure (POF) |
| Authors | Qin, Yingying Zhao, Han Xu, Jianfeng Shi, Yongyong Li, Zhiqiang Qiao, Jie Liu, Jiayin Qin, Chunrong Ren, Chune Li, Jie Chen, Shiling Cao, Yunxia Simpson, Joe Leigh Chen, Zi-Jiang |
| Affiliation | Shandong Univ, Ctr Reprod Med, Prov Hosp,Key Lab Reprod Endocrinol,Minst Educ,Sh, Natl Res Ctr Assisted Reprod Technol & Reprod Gen, Jinan 250021, Peoples R China. Fudan Univ, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China. Shanghai Jiao Tong Univ, BioX Ctr, Shanghai 200240, Peoples R China. Peking Univ, Dept Obstet & Gynecol, Hosp 3, Key Lab Assisted Reprod,Minist Educ, Beijing 100191, Peoples R China. Nanjing Med Univ, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China. Maternal & Child Hlth Hosp, Shenzhen 518028, Peoples R China. Weifang Med Coll, Ctr Reprod Med, Weifang 261053, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China. Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China. Anhui Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Hefei 230032, Peoples R China. Florida Int Univ, Coll Med, Miami, FL 33199 USA. 324 Jingwu Rd, Jinan 250021, Peoples R China. |
| Keywords | GENOME-WIDE ASSOCIATION X-CHROMOSOME CAMPOMELIC DYSPLASIA MUTATIONAL ANALYSIS RECEPTOR GENE SEX REVERSAL WOMEN SOX9 DYSGENESIS VARIANTS |
| Issue Date | 2012 |
| Publisher | human molecular genetics |
| Citation | HUMAN MOLECULAR GENETICS.2012,21,(2),430-436. |
| Abstract | Premature ovarian failure (POF) is a complex heritable disorder known to be caused by chromosomal abnormalities and to date a limited number of known mutations, often autosomal. We sought to identify additional genetic loci associated with POF by performing the first large-scale genome-wide association study (GWAS). GWAS, using Affymetrix SNP 6.0 chip, was conducted in an initial discovery set of 391 well-documented (follicle-stimulating hormone >40 IU/ml) Chinese Han POF patients, compared with 895 unrelated Chinese female controls. A replication study on the most significant loci was then performed in an independent set of 400 cases and 800 controls. Suggestive significant associations were observed at 8q22.3. Replication of eight single-nucleotide polymorphisms (SNPs) (rs10464815, rs10808365, rs3847152, rs3847153, rs3847154, rs3843552, rs10955242, rs3843555) (P <= 3.86 x 10(-6)) was confirmed in verification sets. No specific candidate gene was found in the immediate region of 8q22.3. This GWAS, involving by far the largest sample of POF cases accumulated to date, revealed heretofore unrecognized association between POF and a novel genetic locus or region of unknown nature on 8q22.3. We speculate existence of a long-distance regulatory region that has relevance to the control of ovarian differentiation or oogenesis. Given failure to find association with any of the other autosomal regions known to harbor genes causing ovarian failure, our findings also underscore the likelihood of considerable genetic and etiologic heterogeneity in POF and the need for additional approaches like whole-genome sequencing. |
| URI | http://hdl.handle.net/20.500.11897/393771 |
| ISSN | 0964-6906 |
| DOI | 10.1093/hmg/ddr462 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
