Low bone mineral density is associated with gray matter volume decrease in UK Biobank

Kalc, Polona; Dahnke, Robert; Hoffstaedter, Felix; Gaser, Christian

doi:10.3389/fnagi.2023.1287304

Cited by 4 publications

References 58 publications

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Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Liu,

Xiong

et al. 2024

Alzheimer's & Dementia

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Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain‐derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone‐derived hormones, bone marrow‐derived cells, bone‐derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment.Highlights The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis. Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms. Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.

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Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Liu,

Xiong

et al. 2024

Alzheimer's & Dementia

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Confounder control in biomedicine necessitates conceptual considerations beyond statistical evaluations

Komeyer,

Eickhoff,

Grefkes

et al. 2024

Preprint

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Artificial intelligence holds promise for individualized medicine. Yet, transitioning models from prototyping to clinical applications poses challenges, with confounders being a significant hurdle. We introduce a two-dimensional confounder framework (Confound Continuum), integrating a statistical dimension with a biomedical perspective. Informed and context-sensitive confounder decisions are indispensable for accurate model building, rigorous evaluation and valid interpretation. Using prediction of hand grip strength (HGS) from neuroimaging-derived features in a large sample as an example task, we develop a conceptual framework for confounder considerations and integrate it with an exemplary statistical investigation of 130 candidate confounders. We underline the necessity for conceptual considerations by predicting HGS with varying confound removal scenarios, neuroimaging derived features and machine learning algorithms. We use the confounders alone as features or together with grey matter volume to dissect the contribution of the two signal sources. The conceptual confounder framework distinguishes between high-performance models and pure link models that aim to deepen our understanding of feature-target relationships. The biological attributes of different confounders can overlap to varying degrees with those of the predictive problem space, making the development of pure link models increasingly challenging with greater overlap. The degree of biological overlap allows to sort potential confounders on a conceptual Confound Continuum. This conceptual continuum complements statistical investigations with biomedical domain-knowledge, represented as an orthogonal two-dimensional grid. Exemplary HGS predictions highlighted the substantial impact of confounders on predictive performance. In contrast, choice of features or learning algorithms had considerably smaller influences. Notably, models using confounders as features often outperformed models relying solely on neuroimaging features. Our study provides a confounder framework that combines a statistical perspective on confounders and a biomedical perspective. It stresses the importance of domain expertise in predictive modelling for critical and deliberate interpretation and employment of predictive models in biomedical applications and research.

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Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density

Sha,

Zhang,

Zhao

et al. 2024

The Journal of Clinical Endocrinology &Amp; Metabolism

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Background 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). 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 = 0.95), a significant local signal was discovered at 5p11-5q11.9. Two-sample Mendelian randomization (MR) indicated no causal association in the overall population (β = 0.003, 95% CI = −0.04∼0.03, P = 0.93), while positive causal effects were observed in males (β = 0.005, 95% CI = 0.00∼0.01, P = 0.03) and the elderly (β = 0.009, 95% CI = 0.00∼0.02, P = 0.01) according to one-sample MR. A total of 49 pleiotropic SNPs, with 4 novel SNPs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exo-/endocrine and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes. Conclusions This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among males and the elderly. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.

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Low bone mineral density is associated with gray matter volume decrease in UK Biobank

Cited by 4 publications

References 58 publications

Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Confounder control in biomedicine necessitates conceptual considerations beyond statistical evaluations

Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density

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