Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study.

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Bin Guo, Chao Wang, Yong Zhu, Zhi Liu, Haitao Long, Zhe Ruan, Zhangyuan Lin, Zhihua Fan, Yusheng Li, Shushan Zhao
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引用次数: 2

Abstract

In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs "Volume of normalized brain," "Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis," "Volume of Estimated Total Intra Cranial" and "Volume-ratio of brain segmentation/estimated total intracranial" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.

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大脑结构与骨密度的因果关系:一项大规模的遗传相关性研究。
在这项研究中,我们旨在研究大脑结构与骨密度(BMD)的因果关系。基于英国生物银行对1325种大脑结构脑成像衍生表型(BIDP)的全基因组关联研究(GWAS)汇总统计,以及GEFOS联盟对5个BMD位置(包括全身、股骨颈、腰椎、前臂和脚跟)的GWAS汇总数据集,进行连锁不平衡评分回归(LDSC)来确定遗传相关性,然后进行孟德尔随机化(MR)来探索BIDP与BMD之间的因果关系。进行了几项敏感性分析,以验证目前MR结果的强度和稳定性。为了增加对我们研究结果的信心,我们还在BIDP和骨质疏松症之间进行了验证性MR。LDSC显示,1.93%的BIDP具有错误发现率(FDR)
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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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