Context: A recent genome-wide association study (GWAS) has identified three susceptibility loci (8p32.1, 11p14.1, and 9q22.32) for polycystic ovary syndrome (PCOS) in women of European ancestry. The 9q22.32 locus was previously found in our Chinese PCOS GWAS. Replication of the other two loci is necessary to determine whether the same variants confer risk to PCOS in Han Chinese women.
Objective: This study aimed to investigate the effect of the European GWAS loci on PCOS susceptibility in Han Chinese women.
Design, setting, and patients: This was a genetic association study at a university hospital in composed of 1601 PCOS cases and 1238 age-matched controls. Interventions and Main Outcome Measure: After screening of the regions that cover 500 kb upstream and downstream of the two single-nucleotide polymorphisms (SNPs) using our previous Chinese GWAS data, rs11031010, located in the region of follicle-stimulating hormone B polypeptide (FSHB) gene, was selected for further replication. The other SNPs near rs804279 (GATA4/NEIL2) were excluded based on our previous GWAS data. Then, the variant rs11031010 was genotyped in an independent cohort and the associations with PCOS, endocrine and metabolic traits were assessed.
Results: In the current replication study, rs11031010 was associated with PCOS in Han Chinese women (P = 2.76 × 10(-3)), even after adjustment for age and body mass index. Meta-analysis with our previous GWAS data showed that the allele frequency difference of rs11031010 between PCOS and controls reached genome-wide significance (P = 4.27 × 10(-8)). PCOS women with AA and AC genotypes had a significantly higher LH level than individuals carrying the CC genotype (P =1.60 × 10(-4)). The genetic risk score based on sixteen total Chinese PCOS-risk SNPs, calculated by total number of risk alleles for each subject, was associated with the diagnosis of PCOS (P < 1.00 × 10(-4)).
Conclusions: Variants in FSHB gene are associated with PCOS and LH levels in Han Chinese women. FSHB is thus likely to play an important role in the etiology of PCOS, regardless of ethnicity.