Feng Shuo, Wang Han, Yan Yumeng, Su Xin, Ao Jintao, Chen Wei
Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing, China.
Key Laboratory for Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
Front Genet. 2021 Nov 18;12:756957. doi: 10.3389/fgene.2021.756957. eCollection 2021.
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 ( = 341) were recruited and divided into a discovery group ( = 150) and a replication group ( = 191). GWAS was performed, with T-score as the quantitative trait, using linear regression. Our results revealed that an SNP cluster upstream of showed a trend of association with BMD in Chinese PMO patients. The leading SNP of the cluster was rs475011 ( = 1.15 × 10, beta = 0.51), which is a splicing quantitative trait locus (sQTL) of . This association was further supported by data from the UK Biobank (UKBB; = 9.56 × 10). The high BMD-associated allele G of rs475011 is related to a high intron excision ratio. This SNP may increase BMD by upregulating mature mRNA, based on data from the Genotype-Tissue Expression (GTEx) database. We identified BMD-associated SNPs that regulate in Chinese PMO patients. Future functional experiments are needed to further link rs475011, , and PMO in Chinese individuals.
绝经后骨质疏松症（PMO）是中国老年女性中最常见的骨骼疾病。尽管遗传因素已被证明在PMO中起关键作用，但针对中国人群中与PMO相关的基因位点的研究仍然匮乏。我们旨在通过开展一项全基因组关联研究（GWAS）来识别在中国人群中导致PMO的单核苷酸多态性（SNP）。对绝经后中国女性的骨密度（BMD）进行了评估。招募了T值＜-2.5标准差的参与者（n = 341），并将其分为发现组（n = 150）和复制组（n = 191）。以T值作为数量性状，采用线性回归进行GWAS。我们的结果显示，[基因名称]上游的一个SNP簇在中国PMO患者中显示出与BMD的关联趋势。该簇的主要SNP是rs475011（p = 1.15 × 10，β = 0.51），它是[基因名称]的一个剪接数量性状位点（sQTL）。英国生物银行（UKBB）的数据（p = 9.56 × 10）进一步支持了这种关联。rs475011的高BMD相关等位基因G与高内含子切除率相关。根据基因型-组织表达（GTEx）数据库的数据，该SNP可能通过上调成熟的[基因名称]mRNA来增加BMD。我们在中国PMO患者中鉴定出了调节[基因名称]的BMD相关SNP。未来需要进行功能实验，以进一步将rs475011、[基因名称]和中国人群中的PMO联系起来。
