Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients

Postmenopausal osteoporosis (PMO) is the most common bone disorder in elderly Chinese women. Although genetic factors have been shown to have a pivotal role in PMO, studies on genetic loci associated with PMO in Chinese individuals are still lacking. We aimed to identify SNPs that contribute to PMO...

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Autores principales:	Shuo Feng, Han Wang, Yumeng Yan, Xin Su, Jintao Ao, Wei Chen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	bone mineral density postmenopausal osteoporosis genome-wide association study RREB1 splicing quantitative trait locus Genetics QH426-470
Acceso en línea:	https://doaj.org/article/7da27b56fed64b6e9ed776a7d93a6a34
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spelling	oai:doaj.org-article:7da27b56fed64b6e9ed776a7d93a6a342021-11-18T09:46:06ZRegulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients1664-802110.3389/fgene.2021.756957https://doaj.org/article/7da27b56fed64b6e9ed776a7d93a6a342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.756957/fullhttps://doaj.org/toc/1664-8021Postmenopausal osteoporosis (PMO) is the most common bone disorder in elderly Chinese women. Although genetic factors have been shown to have a pivotal role in PMO, studies on genetic loci associated with PMO in Chinese individuals are still lacking. We aimed to identify SNPs that contribute to PMO in Chinese individuals by conducting a genome-wide association study (GWAS). Bone mineral density (BMD) of postmenopausal Chinese women was assessed. Participants with T-score < −2.5 standard deviations (n = 341) were recruited and divided into a discovery group (n = 150) and a replication group (n = 191). GWAS was performed, with T-score as the quantitative trait, using linear regression. Our results revealed that an SNP cluster upstream of RREB1 showed a trend of association with BMD in Chinese PMO patients. The leading SNP of the cluster was rs475011 (pcombined = 1.15 × 10−6, beta = 0.51), which is a splicing quantitative trait locus (sQTL) of RREB1. This association was further supported by data from the UK Biobank (UKBB; p = 9.56 × 10−12). The high BMD-associated allele G of rs475011 is related to a high intron excision ratio. This SNP may increase BMD by upregulating mature RREB1 mRNA, based on data from the Genotype-Tissue Expression (GTEx) database. We identified BMD-associated SNPs that regulate RREB1 in Chinese PMO patients. Future functional experiments are needed to further link rs475011, RREB1, and PMO in Chinese individuals.Shuo FengHan WangYumeng YanXin SuJintao AoWei ChenFrontiers Media S.A.articlebone mineral densitypostmenopausal osteoporosisgenome-wide association studyRREB1splicing quantitative trait locusGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone mineral density postmenopausal osteoporosis genome-wide association study RREB1 splicing quantitative trait locus Genetics QH426-470
spellingShingle	bone mineral density postmenopausal osteoporosis genome-wide association study RREB1 splicing quantitative trait locus Genetics QH426-470 Shuo Feng Han Wang Yumeng Yan Xin Su Jintao Ao Wei Chen Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients
description	Postmenopausal osteoporosis (PMO) is the most common bone disorder in elderly Chinese women. Although genetic factors have been shown to have a pivotal role in PMO, studies on genetic loci associated with PMO in Chinese individuals are still lacking. We aimed to identify SNPs that contribute to PMO in Chinese individuals by conducting a genome-wide association study (GWAS). Bone mineral density (BMD) of postmenopausal Chinese women was assessed. Participants with T-score < −2.5 standard deviations (n = 341) were recruited and divided into a discovery group (n = 150) and a replication group (n = 191). GWAS was performed, with T-score as the quantitative trait, using linear regression. Our results revealed that an SNP cluster upstream of RREB1 showed a trend of association with BMD in Chinese PMO patients. The leading SNP of the cluster was rs475011 (pcombined = 1.15 × 10−6, beta = 0.51), which is a splicing quantitative trait locus (sQTL) of RREB1. This association was further supported by data from the UK Biobank (UKBB; p = 9.56 × 10−12). The high BMD-associated allele G of rs475011 is related to a high intron excision ratio. This SNP may increase BMD by upregulating mature RREB1 mRNA, based on data from the Genotype-Tissue Expression (GTEx) database. We identified BMD-associated SNPs that regulate RREB1 in Chinese PMO patients. Future functional experiments are needed to further link rs475011, RREB1, and PMO in Chinese individuals.
format	article
author	Shuo Feng Han Wang Yumeng Yan Xin Su Jintao Ao Wei Chen
author_facet	Shuo Feng Han Wang Yumeng Yan Xin Su Jintao Ao Wei Chen
author_sort	Shuo Feng
title	Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients
title_short	Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients
title_full	Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients
title_fullStr	Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients
title_full_unstemmed	Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients
title_sort	regulatory snp of rreb1 is associated with bone mineral density in chinese postmenopausal osteoporosis patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7da27b56fed64b6e9ed776a7d93a6a34
work_keys_str_mv	AT shuofeng regulatorysnpofrreb1isassociatedwithbonemineraldensityinchinesepostmenopausalosteoporosispatients AT hanwang regulatorysnpofrreb1isassociatedwithbonemineraldensityinchinesepostmenopausalosteoporosispatients AT yumengyan regulatorysnpofrreb1isassociatedwithbonemineraldensityinchinesepostmenopausalosteoporosispatients AT xinsu regulatorysnpofrreb1isassociatedwithbonemineraldensityinchinesepostmenopausalosteoporosispatients AT jintaoao regulatorysnpofrreb1isassociatedwithbonemineraldensityinchinesepostmenopausalosteoporosispatients AT weichen regulatorysnpofrreb1isassociatedwithbonemineraldensityinchinesepostmenopausalosteoporosispatients
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Regulatory SNP of RREB1 is Associated With Bone Mineral Density in Chinese Postmenopausal Osteoporosis Patients

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