Family-based analysis of eight susceptibility loci in polycystic ovary syndrome

Shigang Zhao; Ye Tian; Xuan Gao; Xiuqing Zhang; Hongbin Liu; Li You; Yongzhi Cao; Shizhen Su; Wai-Yee Chan; Yun Sun; Han Zhao; Zi-Jiang Chen

doi:10.1038/srep12619

Family-based analysis of eight susceptibility loci in polycystic ovary syndrome

Sci Rep. 2015 Jul 29:5:12619. doi: 10.1038/srep12619.

Authors

Shigang Zhao¹, Ye Tian², Xuan Gao³, Xiuqing Zhang³, Hongbin Liu⁴, Li You³, Yongzhi Cao³, Shizhen Su³, Wai-Yee Chan⁵, Yun Sun², Han Zhao³, Zi-Jiang Chen¹

Affiliations

¹ 1] Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China [2] Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
² Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
³ Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
⁴ 1] Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China; The Key laboratory for Reproductive Endocrinology of Ministry of Education, China; Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China [2] The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁵ The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

Abstract

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that is proposed to have a genetic basis. A recent genome-wide association study (GWAS) identified eight new risk loci that are independently associated with PCOS. To further validate the findings, a total of 321 case-parent trios (963 participants) who had a proband affected with PCOS were recruited for the family-based study. The transmission disequilibrium test (TDT) was used to analyze associations between PCOS and ten single nucleotide polymorphisms (SNPs) mapped to eight new susceptibility loci. Significant differences in transmission were observed for the SNPs rs2349415 (located in the FSHR gene, P = 0.0001) and rs3802457 (located in the C9orf3 gene, P = 0.0001), even after correction for multiple testing bias. The present data provides further evidence for an association between two susceptibility loci, 2p16.3 and 9q22.32, and PCOS. Follow-up functional studies on the FSHR and C9orf3 genes are required to understand their roles in PCOS development.

MeSH terms

Adult
Alleles
Aminopeptidases / genetics
Family Health*
Female
Gene Frequency
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study / methods*
Genotype
Humans
Linkage Disequilibrium
Male
Polycystic Ovary Syndrome / genetics*
Polymorphism, Single Nucleotide*
Receptors, FSH / genetics
Risk Factors
Young Adult

Substances

Receptors, FSH
AOPEP protein, human
Aminopeptidases