Yang Xinyue, Xiao Rui, Liu Beizhong, Xie Bo, Yang Zhao
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing Medical University, China.
Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing Medical University, China.
Exp Gerontol. 2025 Apr;202:112715. doi: 10.1016/j.exger.2025.112715. Epub 2025 Feb 22.
We used Mendelian randomization (MR) approach to examine whether genetically determined inflammation-related risk factors play a role in the onset of osteoporosis (OP) in the European population.
Genome-wide association studies (GWASs) summary statistics of estimated bone mineral density (eBMD) obtained from the public database GEnetic Factors for OSteoporosis Consortium (GEFOS) including 142,487 European people. For exposures, we utilized GWAS data of 9 risk factors including diseases chronic kidney disease (CKD) (41,395 cases and 439,303 controls), type 2 diabetes (T2D) (88,427 cases and 566,778 controls), Alzheimer's disease (AD) (71,880 cases, 383,378 controls) and major depression disorder (MDD) (9240 cases and 9519 controls) and lifestyle behaviors are from different consortiums. Inverse variance weighted (IVW) analysis was principal method in this study and random effect model was applied; MR-Egger method and weighted median method were also performed for reliable results. Cochran's Q test and MR-Egger regression were used to detect heterogeneity and pleiotropy and leave-one-out analysis was performed to find out whether there are influential SNPs.
We found that T2D (IVW: β = 0.05, P = 0.0014), FI (IVW: β = -0.22, P < 0.001), CKD (IVW: β = 0.02, P = 0.009), ALZ (IVW: β = 0.06, P = 0.005), Coffee consumption (IVW: β = 0.11, P = 0.003) were causally associated with OP (P<0.006after Bonferroni correction).
Our study revealed that T2D, FI, CKD, ALZ and coffee consumption are causally associated with OP. Future interventions targeting factors above could provide new clinical strategies for the personalized prevention and treatment of osteoporosis.
我们采用孟德尔随机化（MR）方法，研究基因决定的炎症相关危险因素是否在欧洲人群骨质疏松症（OP）的发病中起作用。
从公共数据库骨质疏松症遗传因素联盟（GEFOS）获得的估计骨密度（eBMD）的全基因组关联研究（GWAS）汇总统计数据，包括142487名欧洲人。对于暴露因素，我们利用了9种危险因素的GWAS数据，包括慢性肾病（CKD）（41395例病例和439303例对照）、2型糖尿病（T2D）（88427例病例和566778例对照）、阿尔茨海默病（AD）（71880例病例、383378例对照）和重度抑郁症（MDD）（9240例病例和9519例对照），生活方式行为数据来自不同的联盟。逆方差加权（IVW）分析是本研究的主要方法，并应用随机效应模型；还进行了MR-Egger方法和加权中位数方法以获得可靠结果。采用Cochran's Q检验和MR-Egger回归检测异质性和多效性，并进行留一法分析以找出是否存在有影响的单核苷酸多态性（SNP）。
我们发现，T2D（IVW：β = 0.05，P = 0.0014）、空腹胰岛素（FI）（IVW：β = -0.22，P < 0.001）、CKD（IVW：β = 0.02，P = 0.009）、AD（IVW：β = 0.06，P = 0.005）、咖啡摄入量（IVW：β = 0.11，P = 0.003）与OP存在因果关系（经Bonferroni校正后P < 0.006）。
我们的研究表明，T2D、FI、CKD、AD和咖啡摄入量与OP存在因果关系。针对上述因素的未来干预措施可为骨质疏松症的个性化预防和治疗提供新的临床策略。
