Department of Orthopaedics, Yueyang Hospital Affiliated of Hunan Normal University, Yueyang, China.
Health Management Center, Yueyang Hospital Affiliated of Hunan Normal University, Yueyang, China.
Medicine (Baltimore). 2024 Sep 6;103(36):e39548. doi: 10.1097/MD.0000000000039548.
The intricate link between childhood obesity and adult osteoporosis has been a subject of numerous clinical inquiries, yet the genetic underpinnings of this association remain enigmatic. Our research aims to unravel the association between adult osteoporosis and childhood obesity using genome-wide association study data for Mendelian randomization (MR) analysis. Utilizing a pool of single-nucleotide polymorphism data associated with childhood obesity obtained from a previous genome-wide association study report involving a study population of 13,848 people in Europe, alongside data of adult osteoporosis sourced from Neale Lab (5266 cases and 331,893 controls). Various methods for MR were used in our research, including weighted mode, simple mode, weighted median, MR-Egger, and the inverse-variance weighted (IVW). We also used Cochran Q test of IVW to assess for heterogeneity, MR-Egger intercept and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis for pleiotropy, and leave-one-out analysis for the result stability. The instrumental variables associated with 11 single-nucleotide polymorphisms were selected. MR analyses unveiled a noteworthy link between genetically forecasted childhood obesity and the onset of adult osteoporosis based on the odds ratio, 95% confidence interval, and P-value from the results of IVW, MR-Egger, weighted median: simple mode, and weighted mode analyses. No significant heterogeneity was found by the assessment using MR-Egger and IVW. Similarly, there was no indication of pleiotropy based on the MR-PRESSO and MR-Egger analyses. Leave-one-out analysis confirmed the stability of the results. Our research suggests that childhood obesity, as predicted by genetic factors, may pose a significant risk for the development of osteoporosis in adulthood.
儿童肥胖与成年骨质疏松症之间的复杂联系一直是许多临床研究的课题，但这种关联的遗传基础仍然是个谜。我们的研究旨在利用孟德尔随机化（MR）分析的全基因组关联研究数据，揭示成年骨质疏松症与儿童肥胖之间的关联。我们使用了先前全基因组关联研究报告中获得的与儿童肥胖相关的单核苷酸多态性数据池，该研究涉及欧洲的 13848 人研究人群，以及 Neale 实验室提供的成年骨质疏松症数据（5266 例病例和 331893 例对照）。我们在研究中使用了各种 MR 方法，包括加权模式、简单模式、加权中位数、MR-Egger 和逆方差加权（IVW）。我们还使用 IVW 的 Cochran Q 检验评估异质性、MR-Egger 截距和 MR-Pleiotropy RESidual Sum and Outlier（MR-PRESSO）分析评估多效性，以及进行单因素剔除分析以评估结果稳定性。选择与 11 个单核苷酸多态性相关的工具变量。MR 分析揭示了基于 IVW、MR-Egger、加权中位数：简单模式和加权模式分析结果的比值比、95%置信区间和 P 值，遗传预测的儿童肥胖与成年骨质疏松症的发病之间存在显著关联。使用 MR-Egger 和 IVW 评估未发现显著异质性。同样，基于 MR-PRESSO 和 MR-Egger 分析，没有多效性的迹象。单因素剔除分析证实了结果的稳定性。我们的研究表明，遗传因素预测的儿童肥胖可能是成年后骨质疏松症发展的一个重要风险因素。
