College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Diseases & Population (DaP) Geninfo Lab, School of Life Sciences, Westlake University, 18 Shilongshan Road, Xihu District, Zhejiang, 310024, Hangzhou, China.
BMC Med. 2022 Oct 4;20(1):361. doi: 10.1186/s12916-022-02531-w.
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.
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.
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; 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; 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), 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, 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). 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).
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.
出生体重不仅被认为会影响未来的生长发育，还会诱发终生疾病；本研究旨在探讨出生体重与成人骨量之间的关系。
我们进行了多变量回归分析，以评估出生体重与双能 X 射线吸收法（DXA）和定量超声（QUS）测量的骨参数之间的关联，这两种方法均为独立分析。我们还实施了系统的孟德尔随机化（MR）分析，以使用胎儿特异性和母体特异性工具变量来探索两者之间的因果关系。
在观察性分析中，我们发现较高的出生体重可能会增加成人的骨面积（腰椎，β 系数=0.17，P<2.00×10；侧位腰椎，β 系数=0.02，P=0.04），降低骨矿物质含量校正后的骨面积（BMCadjArea）（腰椎，β 系数=-0.01，P=2.27×10；侧位腰椎，β 系数=-0.05，P=0.001）和成人骨密度（BMD）（腰椎，β 系数=-0.04，P=0.007；侧位腰椎，β 系数=-0.03，P=0.02；跟骨，β 系数=-0.06，P<2.00×10），并且我们观察到出生体重对骨大小的影响大于对 BMC 的影响。在 MR 分析中，发现较高的胎儿特异性遗传决定的出生体重与较高的骨面积有关（腰椎；β 系数=0.15，P=1.26×10，总髋部，β 系数=0.15，P=0.005；转子间区，β 系数=0.13，P=0.0009；转子区，β 系数=0.11，P=0.03），但 BMD 较低（腰椎，β 系数=-0.10，P=0.01；侧位腰椎，β 系数=-0.12，P=0.0003，跟骨β 系数=-0.11，P=3.33×10）。此外，我们发现较高的母体特异性遗传决定的后代出生体重与后代成人跟骨 BMD 较低有关（β 系数=-0.001，P=0.04）。
观察性分析表明，较高的出生体重与成人骨面积增加但 BMD 降低有关。通过利用具有母体和胎儿特异性出生体重影响的遗传工具变量，观察到的关系可以通过胎儿的直接遗传效应和母体的间接遗传效应来反映。
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