Childhood obesity influences mid-to-late life bone health through shared genetic architecture

IF 3.6 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Bone Pub Date : 2025-09-09 DOI:10.1016/j.bone.2025.117639

Maoyao Xia , Yang Qu , Bowen Lei , Yangdan Zhong , Tao Han , Linna Sha , Jiangbo Zhu , Xin Song , Bin Yang , Qin Deng , Jiaojiao Hou , Sirui Zheng , Rong Xiang , Xunying Zhao , Ting Yu , Jinyu Zhou , Mengyu Fan , Xia Jiang

{"title":"Childhood obesity influences mid-to-late life bone health through shared genetic architecture","authors":"Maoyao Xia , Yang Qu , Bowen Lei , Yangdan Zhong , Tao Han , Linna Sha , Jiangbo Zhu , Xin Song , Bin Yang , Qin Deng , Jiaojiao Hou , Sirui Zheng , Rong Xiang , Xunying Zhao , Ting Yu , Jinyu Zhou , Mengyu Fan , Xia Jiang","doi":"10.1016/j.bone.2025.117639","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Despite higher body mass index (BMI) in adulthood being widely acknowledged as protective for bone mineral density (BMD), the effect of childhood BMI on adult BMD remains inconclusive. This study aims to elucidate the shared genetic basis underlying childhood BMI and adult heel estimated BMD (eBMD).</div></div><div><h3>Methods</h3><div>We conducted a comprehensive genome-wide cross-trait analysis to determine the genetic correlations, pleiotropic loci, and causal relationships between childhood BMI and adult eBMD. Summary statistics were collected from the hitherto largest available genome-wide association studies conducted for childhood BMI (<em>N</em> = 62,026) and adult eBMD (<em>N</em> = 426,824) of European individuals.</div></div><div><h3>Results</h3><div>A significant positive overall genetic correlation was observed for childhood BMI and adult eBMD (<span><math><msub><mi>r</mi><mi>g</mi></msub></math></span> = 0.09, <em>P</em> = 4.00 × 10<sup>−4</sup>), which was supported by the significant local signal observed in one genomic region (5q21.3). The shared genetic basis was further emphasized by 55 pleiotropic loci identified through the cross-trait meta-analysis, 11 shared gene-tissue pairs observed in transcriptome-wide association study, and a robust causal relationship demonstrated by Mendelian randomization (<span><math><mi>β</mi></math></span> = 0.12, 95 %CIs = 0.06–0.18).</div></div><div><h3>Conclusions</h3><div>Our work highlights the substantial shared genetic influence and putative causal link underlying childhood BMI and mid-to-late life eBMD, offering new avenues for personalized prevention strategies against osteoporosis.</div></div><div><h3>Trial registration</h3><div>Not applicable.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117639"},"PeriodicalIF":3.6000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S8756328225002510","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Despite higher body mass index (BMI) in adulthood being widely acknowledged as protective for bone mineral density (BMD), the effect of childhood BMI on adult BMD remains inconclusive. This study aims to elucidate the shared genetic basis underlying childhood BMI and adult heel estimated BMD (eBMD).

Methods

We conducted a comprehensive genome-wide cross-trait analysis to determine the genetic correlations, pleiotropic loci, and causal relationships between childhood BMI and adult eBMD. Summary statistics were collected from the hitherto largest available genome-wide association studies conducted for childhood BMI (N = 62,026) and adult eBMD (N = 426,824) of European individuals.

Results

A significant positive overall genetic correlation was observed for childhood BMI and adult eBMD (

r_{g}

= 0.09, P = 4.00 × 10⁻⁴), which was supported by the significant local signal observed in one genomic region (5q21.3). The shared genetic basis was further emphasized by 55 pleiotropic loci identified through the cross-trait meta-analysis, 11 shared gene-tissue pairs observed in transcriptome-wide association study, and a robust causal relationship demonstrated by Mendelian randomization (

β

= 0.12, 95 %CIs = 0.06–0.18).

Conclusions

Our work highlights the substantial shared genetic influence and putative causal link underlying childhood BMI and mid-to-late life eBMD, offering new avenues for personalized prevention strategies against osteoporosis.

Trial registration

Not applicable.

查看原文本刊更多论文

儿童肥胖通过共享的遗传结构影响中晚期的骨骼健康。

背景：尽管成年期较高的身体质量指数（BMI）被广泛认为对骨密度（BMD）有保护作用，但儿童期BMI对成年期骨密度的影响尚不明确。本研究旨在阐明儿童BMI和成人脚跟估计BMD （eBMD）的共同遗传基础。方法：我们进行了一项全面的全基因组交叉性状分析，以确定儿童BMI和成人eBMD之间的遗传相关性、多效位点和因果关系。汇总统计数据来自迄今为止最大的欧洲个体儿童BMI （N = 62,026）和成人eBMD （N = 426,824）全基因组关联研究。结果：儿童BMI与成人eBMD总体呈显著正遗传相关（rg = 0.09,P = 4.00 × 10-4），这得到了一个基因组区域显著局部信号（5q21.3）的支持。通过跨性状荟萃分析鉴定出55个多性状位点，在转录组全关联研究中观察到11个共享基因-组织对，以及孟德尔随机化（β = 0.12,95 %CIs = 0.06-0.18）证实了强有力的因果关系，进一步强调了共同的遗传基础。结论：我们的工作强调了儿童BMI和中老年eBMD之间的重大共同遗传影响和假定的因果关系，为骨质疏松症的个性化预防策略提供了新的途径。试验注册：不适用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Bone 医学-内分泌学与代谢

CiteScore

8.90

自引率

4.90%

发文量

264

审稿时长

30 days

期刊介绍： BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.