10.6084/M9.FIGSHARE.C.6230326.V1
Jiang-Wei Xia
Jiang-Wei
Xia
Zhejiang University
Westlake University
Lin Zhang
Lin
Zhang
Hangzhou Women’s Hospital
Jin Li
Jin
Li
Hangzhou Women’s Hospital
Cheng-Da Yuan
Cheng-Da
Yuan
Hangzhou Hospital of Traditional Chinese Medicine
Xiao-Wei Zhu
Xiao-Wei
Zhu
Westlake University
Yu Qian
Yu
Qian
Westlake University
Saber Khederzadeh
Saber
Khederzadeh
Westlake University
Jia-Xuan Gu
Jia-Xuan
Gu
Zhejiang University
Westlake University
Lin Xu
Lin
Xu
Binzhou Medical University
Jian-Hua Gao
Jian-Hua
Gao
Nanchang University
Ke-Qi Liu
Ke-Qi
Liu
Nanchang University
David Karasik
David
Karasik
Bar-Ilan University
Shu-Yang Xie
Shu-Yang
Xie
Binzhou Medical University
Guo-Bo Chen
Guo-Bo
Chen
Hou-Feng Zheng
Hou-Feng
Zheng
0000-0001-5681-8598
Zhejiang University
Westlake University
Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass
Abstract Background Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass. Methods We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the causal association between them with both fetal-specific and maternal-specific instrumental variables. Results In the observational analyses, we found that higher birth weight could increase the adult bone area (lumbar spine, β-coefficient= 0.17, P < 2.00 × 10−16; lateral spine, β-coefficient = 0.02, P = 0.04), decrease bone mineral content-adjusted bone area (BMCadjArea) (lumbar spine, β-coefficient= − 0.01, P = 2.27 × 10−14; lateral spine, β-coefficient = − 0.05, P = 0.001), and decrease adult bone mineral density (BMD) (lumbar spine, β-coefficient = − 0.04, P = 0.007; lateral spine; β-coefficient = − 0.03, P = 0.02; heel, β-coefficient = − 0.06, P < 2.00 × 10−16), and we observed that the effect of birth weight on bone size was larger than that on BMC. In MR analyses, the higher fetal-specific genetically determined birth weight was identified to be associated with higher bone area (lumbar spine; β-coefficient = 0.15, P = 1.26 × 10−6, total hip, β-coefficient = 0.15, P = 0.005; intertrochanteric area, β-coefficient = 0.13, P = 0.0009; trochanter area, β-coefficient = 0.11, P = 0.03) but lower BMD (lumbar spine, β-coefficient = − 0.10, P = 0.01; lateral spine, β-coefficient = − 0.12, P = 0.0003, and heel β-coefficient = − 0.11, P = 3.33 × 10−13). In addition, we found that the higher maternal-specific genetically determined offspring birth weight was associated with lower offspring adult heel BMD (β-coefficient = − 0.001, P = 0.04). Conclusions The observational analyses suggested that higher birth weight was associated with the increased adult bone area but decreased BMD. By leveraging the genetic instrumental variables with maternal- and fetal-specific effects on birth weight, the observed relationship could be reflected by both the direct fetal and indirect maternal genetic effects.
Biophysics
Medicine
Cell Biology
Physiology
Biotechnology
Ecology
Sociology
Biological Sciences not elsewhere classified
Science Policy
figshare
2022
2022-10-04
2022-10-04
Collection
10.6084/m9.figshare.c.6230326
CC BY 4.0