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

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 d...

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Main Authors: Bin Guo, Chao Wang, Yong Zhu, Zhi Liu, Haitao Long, Zhe Ruan, Zhangyuan Lin, Zhihua Fan, Yusheng Li, Shushan Zhao
Format: Article
Language:English
Published: Nature Publishing Group 2023-07-01
Series:Bone Research
Online Access:https://doi.org/10.1038/s41413-023-00270-z
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author Bin Guo
Chao Wang
Yong Zhu
Zhi Liu
Haitao Long
Zhe Ruan
Zhangyuan Lin
Zhihua Fan
Yusheng Li
Shushan Zhao
author_facet Bin Guo
Chao Wang
Yong Zhu
Zhi Liu
Haitao Long
Zhe Ruan
Zhangyuan Lin
Zhihua Fan
Yusheng Li
Shushan Zhao
author_sort Bin Guo
collection DOAJ
description 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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spelling doaj.art-33aed4ec9a974528a6d6360e299e875d2023-07-23T11:09:05ZengNature Publishing GroupBone Research2095-62312023-07-0111111210.1038/s41413-023-00270-zCausal associations of brain structure with bone mineral density: a large-scale genetic correlation studyBin Guo0Chao Wang1Yong Zhu2Zhi Liu3Haitao Long4Zhe Ruan5Zhangyuan Lin6Zhihua Fan7Yusheng Li8Shushan Zhao9Department of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Dermatology, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityDepartment of Orthopedics, Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1038/s41413-023-00270-z
spellingShingle Bin Guo
Chao Wang
Yong Zhu
Zhi Liu
Haitao Long
Zhe Ruan
Zhangyuan Lin
Zhihua Fan
Yusheng Li
Shushan Zhao
Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study
Bone Research
title Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study
title_full Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study
title_fullStr Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study
title_full_unstemmed Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study
title_short Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study
title_sort causal associations of brain structure with bone mineral density a large scale genetic correlation study
url https://doi.org/10.1038/s41413-023-00270-z
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