title: Association of 8q22.3 locus in Chinese Han with idiopathic premature ovarian failure (POF).
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 × 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.
authors: Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, 324 Jingwu Road, Jinan 250021, China.
authors: Yingying
authors: Y
authors: Qin
authors: Han
authors: H
authors: Zhao
authors: Jianfeng
authors: J
authors: Xu
authors: Yongyong
authors: Y
authors: Shi
authors: Zhiqiang
authors: Z
authors: Li
authors: Jie
authors: J
authors: Qiao
authors: Jiayin
authors: J
authors: Liu
authors: Chunrong
authors: C
authors: Qin
authors: Chune
authors: C
authors: Ren
authors: Jie
authors: J
authors: Li
authors: Shiling
authors: S
authors: Chen
authors: Yunxia
authors: Y
authors: Cao
authors: Joe Leigh
authors: JL
authors: Simpson
authors: Zi-Jiang
authors: ZJ
authors: Chen
mesh_terms: D016022:Case-Control Studies; D002681:China; D002898:Chromosomes, Human, Pair 8; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*