Abstract
To date, eleven genome-wide significant (GWS) loci (P < 5×10−8) for polycystic ovary syndrome (PCOS) have been identified through genome-wide association studies (GWAS). Some of the risk loci have been selected for replications and validated in multiple ethnicities, however, few previous studies investigated all loci. Scanning all the GWAS variants would demonstrate a more informative profile of variance they explained. Thus, we analyzed all the 17 single nucleotide polymorphisms (SNPs) mapping to the 11 GWAS loci in an independent sample set of 800 Chinese subjects with PCOS and 1110 healthy controls systematically. Variants of rs3802457 in C9orf3 locus (P = 5.99×10−4) and rs13405728 in LHCGR locus (P = 3.73×10−4) were significantly associated with PCOS after the strict Bonferroni correction in our data set. The further haplotype analysis indicated that in the block of C9orf3 gene (rs4385527 and rs3802457), GA haplotype played a protective role in PCOS (8.7 vs 5.0, P = 9.85×10−6, OR = 0.548, 95%CI = 0.418–0.717), while GG haplotype was found suffering from an extraordinarily increased risk of PCOS (73.6% vs79.2%, P = 3.41×10−5, OR = 1.394, 95%CI = 1.191–1.632). Moreover, the directions of effects for all SNPs were consistent with previous GWAS reports (P = 1.53×10−5). Polygenic score analysis demonstrated that these 17 SNPs have a significant capacity on predicting case-control status in our samples (P = 7.17×10−9), meanwhile all these gathered 17 SNPs explained about 2.40% of variance. Our findings supported that C9orf3 and LHCGR loci variants were vital susceptibility of PCOS.
Highlights
Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder in reproductive-age women with a prevalence of approximately 5%-10% [1,2]
Two genome-wide association study (GWAS) conducted in Chinese Han population indicated that common variants located in 11 genomic areas were associated with PCOS [8,9]
McAllister et al.[18] predicted that the candidate genes by the PCOS GWAS might comprise a hierarchical signaling network which would influence the theca cell hormone biosynthesis
Summary
Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder in reproductive-age women with a prevalence of approximately 5%-10% [1,2]. The syndrome is defined by clinical or biochemical hyperandrogenism (HA), oligomenorrhea/amenorrhea (O) and polycystic ovaries (PCO) on ultrasonography [3]. It is associated with obesity, infertility and PLOS ONE | DOI:10.1371/journal.pone.0140695. Replication of PCOS Susceptibility Loci in Chinese metabolic complications including impaired glucose tolerance (IGT), insulin resistance (IR) and dyslipidemia etc. It is common with increased risk of endometrial cancer, type 2 diabetes (T2D) and other cardiovascular diseases [4,5,6] which leading to the detrimental impact on women's health. Another recent followup study replicated four of the PCOS susceptibility loci (DENND1A, THADA, FSHR and INSR) in a cohort of European population, and the risk score analysis indicated the vital role in the etiology of PCOS across ethnicities for the susceptibility loci identified in the Chinese GWAS [14]
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