Cargando…

Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population

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 studie...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Yuping, Li, Zhiqiang, Ai, Fenglian, Chen, Jianhua, Xing, Qiong, Zhou, Ping, Wei, Zhaolian, Shi, Yongyong, He, Xiao-Jin, Cao, Yunxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608705/
https://www.ncbi.nlm.nih.gov/pubmed/26474478
http://dx.doi.org/10.1371/journal.pone.0140695
_version_ 1782395700837875712
author Xu, Yuping
Li, Zhiqiang
Ai, Fenglian
Chen, Jianhua
Xing, Qiong
Zhou, Ping
Wei, Zhaolian
Shi, Yongyong
He, Xiao-Jin
Cao, Yunxia
author_facet Xu, Yuping
Li, Zhiqiang
Ai, Fenglian
Chen, Jianhua
Xing, Qiong
Zhou, Ping
Wei, Zhaolian
Shi, Yongyong
He, Xiao-Jin
Cao, Yunxia
author_sort Xu, Yuping
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4608705
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-46087052015-10-29 Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population Xu, Yuping Li, Zhiqiang Ai, Fenglian Chen, Jianhua Xing, Qiong Zhou, Ping Wei, Zhaolian Shi, Yongyong He, Xiao-Jin Cao, Yunxia PLoS One Research Article 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. Public Library of Science 2015-10-16 /pmc/articles/PMC4608705/ /pubmed/26474478 http://dx.doi.org/10.1371/journal.pone.0140695 Text en © 2015 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xu, Yuping
Li, Zhiqiang
Ai, Fenglian
Chen, Jianhua
Xing, Qiong
Zhou, Ping
Wei, Zhaolian
Shi, Yongyong
He, Xiao-Jin
Cao, Yunxia
Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population
title Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population
title_full Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population
title_fullStr Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population
title_full_unstemmed Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population
title_short Systematic Evaluation of Genetic Variants for Polycystic Ovary Syndrome in a Chinese Population
title_sort systematic evaluation of genetic variants for polycystic ovary syndrome in a chinese population
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608705/
https://www.ncbi.nlm.nih.gov/pubmed/26474478
http://dx.doi.org/10.1371/journal.pone.0140695
work_keys_str_mv AT xuyuping systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT lizhiqiang systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT aifenglian systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT chenjianhua systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT xingqiong systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT zhouping systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT weizhaolian systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT shiyongyong systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT hexiaojin systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation
AT caoyunxia systematicevaluationofgeneticvariantsforpolycysticovarysyndromeinachinesepopulation