血清 25-羟维生素 D 与骨矿物质密度之间的共同遗传结构和因果关系。

IF 5 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Linna Sha, Li Zhang, Xunying Zhao, Rong Xiang, Xueyao Wu, Jiangbo Zhu, Jiaojiao Hou, Qin Deng, Chenjiarui Qin, Changfeng Xiao, Yang Qu, Tao Han, Jinyu Zhou, Sirui Zheng, Ting Yu, Xin Song, Bin Yang, Mengyu Fan, Xia Jiang
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引用次数: 0

摘要

背景:尽管维生素 D 在维持骨骼健康方面的调节作用已得到公认,但人们对血清 25- 羟基维生素 D(25OHD)与骨矿物质密度(BMD)之间的共同遗传学和因果关系知之甚少:方法:利用英国生物库(UKB)队列中的个体水平数据,以及对欧洲个体进行的血清25OHD(N = 417,580)和估计足跟骨密度(eBMD,N = 426,824)全基因组关联研究(GWAS)中的汇总水平数据,我们通过全面的全基因组跨性状设计,系统地阐明了血清25OHD和eBMD的共同遗传结构:尽管缺乏整体遗传相关性(rg = -0.001,P = 0.95),但在 5p11-5q11.9 处发现了一个显著的局部信号。双样本孟德尔随机化(MR)表明,在整个人群中没有因果关系(β = 0.003,95% CI = -0.04∼0.03,P = 0.93),而根据单样本 MR,在男性(β = 0.005,95% CI = 0.00∼0.01,P = 0.03)和老年人(β = 0.009,95% CI = 0.00∼0.02,P = 0.01)中观察到正的因果效应。共鉴定出49个多向性SNPs,其中包括4个新型SNPs(rs1077151、rs79873740、rs12150353和rs4760401),共有95个基因-组织对表现出重叠,主要富集在神经、消化、外/内分泌和心血管系统。蛋白质-蛋白质相互作用分析确定 RPS9 和 RPL7A 为枢纽基因:这项研究揭示了提高血清 25OHD 水平以降低男性和老年人骨质疏松症风险的潜在健康益处。该研究还揭示了血清 25OHD 和 eBMD 之间的共同遗传基础,为了解错综复杂的生物通路提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density.

Context: Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD).

Objective: We aimed to investigate the shared genetic architecture and causal relationship between serum 25OHD and BMD, providing insights into their underlying biological mechanisms.

Methods: Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417 580) and estimated heel BMD (eBMD, N = 426 824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design.

Results: Despite a lack of global genetic correlation (rg=-0.001; P = .95), a statistically significant local signal was discovered at 5p11-5q11.9. Two-sample mendelian randomization (MR) indicated no causal association in the overall population (β=.003, 95% CI, -0.04 to 0.03; P = .93), while positive causal effects were observed in males (β=.005, 95% CI, 0.00 to 0.01; P = .03) and older individuals (β=.009, 95% CI, 0.00∼0.02; P = .01) according to one-sample MR. A total of 49 pleiotropic single-nucleotide variations (SNVs), with 4 novel SNVs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exocrine/endocrine, and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes.

Conclusion: This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among men and individuals older than 65 years. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.

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来源期刊
Journal of Clinical Endocrinology & Metabolism
Journal of Clinical Endocrinology & Metabolism 医学-内分泌学与代谢
CiteScore
11.40
自引率
5.20%
发文量
673
审稿时长
1 months
期刊介绍: The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.
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