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Impact of serum calcium levels on total body bone mineral density: A mendelian randomization study in five age strata.

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Sun Jing-Yi[a] * ; Zhang Haihua[b] ; Zhang Yan[c] ; Wang Longcai[d] ; Sun Bao-Liang[e] ; Gao Feng[f,*1] ; Liu Guiyou[b,e,g,h,*2] ;
机构： [a]Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250021, China [b]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, 100069, China [c]Department of Pathology, The Affiliated Hospital of Weifang Medical University, Weifang, 261053, China [d]Department of Anesthesiology, The Affiliated Hospital of Weifang Medical University, Weifang, 261053, China [e]Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Department of Neurology, Second Affiliated Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China [f]Department of Trauma and Emergency Surgeon, The Second Affiliated Hospital, Harbin Medical University, Harbin, China [g]National Engineering Laboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China [h]Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
出处：
DOI： 10.1016/j.clnu.2021.03.012
ISSN：

关键词： Bone mineral density Serum calcium Mendelian randomization Genome-wide association studies

摘要：
Mendelian randomization (MR) studies have reported the causal association between serum calcium levels and bone mineral density (BMD). The results showed that genetically increased serum calcium levels in individuals with normal calcium levels did not increase BMD and could even reduce BMD. However, whether there are differences in the association between serum calcium and BMD in different age strata remains unclear. We selected eight serum calcium genetic variants with genome-wide significance (P < 5.00E-08) as the potential instrumental variables. We conducted an MR analysis to evaluate the impact of serum calcium levels on total body BMD in five age strata, 0-15, 15-30, 30-45, 45-60, and ≥60 years, using large-scale serum calcium (61,079 individuals) and total body BMD genome-wide association study (66,628 individuals) datasets. For pleiotropy analysis, we used a manual method and four common statistical methods, namely the MR-Egger intercept, MR-PRESSO, heterogeneity, and Steiger filtering tests. For MR analysis, we selected four MR methods, namely inverse-variance weighted, weighted median, MR-Egger, and MR-PRESSO. In addition to the univariable MR analysis, we conducted a multivariate MR analysis taking into account the effect of serum parathyroid hormone levels. Univariable MR analysis using the inverse-variance weighted method indicated that per 0.5-mg/dL increase (about 1 standard deviation) in serum calcium levels was statistically significantly associated with reduced total body BMD only in the ≥60 years stratum (effect estimate (beta) = -0.545, 95% confidence interval (CI): -0.892 to -0.198, P = 0.002). The weighted median regression (beta = -0.446, 95% CI: -0.821 to -0.094, P = 1.40E-02) and MR-PRESSO (beta = -0.545, 95% CI: -0.892 to -0.198, P = 0.022) MR methods further supported this suggestive association. The multivariable MR analysis also found a significant association between increased serum calcium levels and reduced total body BMD in the ≥60 years stratum (beta = -0.547, 95% CI: -0.934 to -0.16, P = 0.006). Our results provide genetic evidence that increased serum calcium levels did not improve BMD in the general population and that the elevated serum calcium levels in generally healthy populations, especially in adults older than 60 years, may even reduce the BMD. Our results are comparable with those of recent MR findings. Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

基金：
National Natural Science Foundation of China [grant numbers 82071212, 81901181]; the Mathematical Tianyuan Fund of the National Natural Science Foundation of China [grant number 12026414]; and the Funds of Academic Promotion Programme of Shandong First Medical University &Shandong Academy of Medical Sciences [grant numbers 2019QL016, 2019PT007].
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类 | 2 区 医学
小类 | 1 区 营养学
最新[2023]版：
大类 | 2 区 医学
小类 | 1 区 营养学
JCR分区：
出版当年[2019]版：
Q1 NUTRITION & DIETETICS
最新[2023]版：
Q1 NUTRITION & DIETETICS

影响因子： 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

第一作者：
第一作者机构： [a]Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250021, China
通讯作者：
通讯机构： [b]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, 100069, China [e]Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Department of Neurology, Second Affiliated Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China [f]Department of Trauma and Emergency Surgeon, The Second Affiliated Hospital, Harbin Medical University, Harbin, China [g]National Engineering Laboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China [h]Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China [*1]Department of Trauma and Emergency Surgeon, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. [*2]Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
推荐引用方式(GB/T 7714)：
Sun Jing-Yi,Zhang Haihua,Zhang Yan,et al.Impact of serum calcium levels on total body bone mineral density: A mendelian randomization study in five age strata.[J].CLINICAL NUTRITION.2021,40(5):2726-2733.doi:10.1016/j.clnu.2021.03.012.
APA：
Sun Jing-Yi,Zhang Haihua,Zhang Yan,Wang Longcai,Sun Bao-Liang...&Liu Guiyou.(2021).Impact of serum calcium levels on total body bone mineral density: A mendelian randomization study in five age strata..CLINICAL NUTRITION,40,(5)
MLA：
Sun Jing-Yi,et al."Impact of serum calcium levels on total body bone mineral density: A mendelian randomization study in five age strata.".CLINICAL NUTRITION 40..5(2021):2726-2733

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