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...
| Main Authors: | , , , , , , , , , , , , , , |
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BMC
2022-10-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-022-02531-w |
| _version_ | 1811226704314630144 |
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| author | Jiang-Wei Xia Lin Zhang Jin Li Cheng-Da Yuan Xiao-Wei Zhu Yu Qian Saber Khederzadeh Jia-Xuan Gu Lin Xu Jian-Hua Gao Ke-Qi Liu David Karasik Shu-Yang Xie Guo-Bo Chen Hou-Feng Zheng |
| author_facet | Jiang-Wei Xia Lin Zhang Jin Li Cheng-Da Yuan Xiao-Wei Zhu Yu Qian Saber Khederzadeh Jia-Xuan Gu Lin Xu Jian-Hua Gao Ke-Qi Liu David Karasik Shu-Yang Xie Guo-Bo Chen Hou-Feng Zheng |
| author_sort | Jiang-Wei Xia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:30:51Z |
| format | Article |
| id | doaj.art-fbe50807f3314eedb242b875a6bc5863 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-12T09:30:51Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj.art-fbe50807f3314eedb242b875a6bc58632022-12-22T03:38:23ZengBMCBMC Medicine1741-70152022-10-0120111310.1186/s12916-022-02531-wBoth indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone massJiang-Wei Xia0Lin Zhang1Jin Li2Cheng-Da Yuan3Xiao-Wei Zhu4Yu Qian5Saber Khederzadeh6Jia-Xuan Gu7Lin Xu8Jian-Hua Gao9Ke-Qi Liu10David Karasik11Shu-Yang Xie12Guo-Bo Chen13Hou-Feng Zheng14College of Life Sciences, Zhejiang UniversityHangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital)Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital)Department of Dermatology, Hangzhou Hospital of Traditional Chinese MedicineDiseases & Population (DaP) Geninfo Lab, School of Life Sciences, Westlake UniversityDiseases & Population (DaP) Geninfo Lab, School of Life Sciences, Westlake UniversityDiseases & Population (DaP) Geninfo Lab, School of Life Sciences, Westlake UniversityCollege of Life Sciences, Zhejiang UniversityWBBC Shandong Center, Binzhou Medical UniversityWBBC Jiangxi Center, Jiangxi Medical CollegeWBBC Jiangxi Center, Jiangxi Medical CollegeAzrieli Faculty of Medicine, Bar-Ilan UniversityWBBC Shandong Center, Binzhou Medical UniversityClinical Research Institute, Zhejiang Provincial People’s Hospital, Hangzhou Medical CollegeCollege of Life Sciences, Zhejiang UniversityAbstract 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.https://doi.org/10.1186/s12916-022-02531-wBirth weightBone mineral densityFetal genetic effectsMaternal genetic effectsObservational analysisMendelian randomization |
| spellingShingle | Jiang-Wei Xia Lin Zhang Jin Li Cheng-Da Yuan Xiao-Wei Zhu Yu Qian Saber Khederzadeh Jia-Xuan Gu Lin Xu Jian-Hua Gao Ke-Qi Liu David Karasik Shu-Yang Xie Guo-Bo Chen Hou-Feng Zheng Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass BMC Medicine Birth weight Bone mineral density Fetal genetic effects Maternal genetic effects Observational analysis Mendelian randomization |
| title | Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass |
| title_full | Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass |
| title_fullStr | Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass |
| title_full_unstemmed | Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass |
| title_short | Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass |
| title_sort | both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass |
| topic | Birth weight Bone mineral density Fetal genetic effects Maternal genetic effects Observational analysis Mendelian randomization |
| url | https://doi.org/10.1186/s12916-022-02531-w |
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