Variability in newborn telomere length is explained by inheritance and intrauterine environment
Abstract Background Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine en...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-021-02217-9 |
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| author | Li Chen Karen Tan Mei Ling Min Gong Mary F. F. Chong Kok Hian Tan Yap Seng Chong Michael J. Meaney Peter D. Gluckman Johan G. Eriksson Neerja Karnani |
| author_facet | Li Chen Karen Tan Mei Ling Min Gong Mary F. F. Chong Kok Hian Tan Yap Seng Chong Michael J. Meaney Peter D. Gluckman Johan G. Eriksson Neerja Karnani |
| author_sort | Li Chen |
| collection | DOAJ |
| description | Abstract Background Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus. Methods Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26–28 weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied. Results Longer maternal TL (β = 0.14, P = 1.99E−05) and higher paternal age (β = 0.10, P = 3.73E−03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: P meta = 5.95E−08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother’s TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL. Conclusions Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors. Trial registration ClinicalTrials.gov , NCT01174875. Registered on 1 July 2010 |
| first_indexed | 2024-12-23T11:46:46Z |
| format | Article |
| id | doaj.art-f773bd804fd14d6893d96f568754da2f |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-12-23T11:46:46Z |
| publishDate | 2022-01-01 |
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| series | BMC Medicine |
| spelling | doaj.art-f773bd804fd14d6893d96f568754da2f2022-12-21T17:48:20ZengBMCBMC Medicine1741-70152022-01-0120111710.1186/s12916-021-02217-9Variability in newborn telomere length is explained by inheritance and intrauterine environmentLi Chen0Karen Tan Mei Ling1Min Gong2Mary F. F. Chong3Kok Hian Tan4Yap Seng Chong5Michael J. Meaney6Peter D. Gluckman7Johan G. Eriksson8Neerja Karnani9Singapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARKK Women’s and Children’s HospitalSingapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARSingapore Institute for Clinical Sciences, A*STARAbstract Background Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus. Methods Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26–28 weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied. Results Longer maternal TL (β = 0.14, P = 1.99E−05) and higher paternal age (β = 0.10, P = 3.73E−03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: P meta = 5.95E−08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother’s TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL. Conclusions Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors. Trial registration ClinicalTrials.gov , NCT01174875. Registered on 1 July 2010https://doi.org/10.1186/s12916-021-02217-9NewbornTelomere lengthIntrauterine exposuresInheritanceSex differences |
| spellingShingle | Li Chen Karen Tan Mei Ling Min Gong Mary F. F. Chong Kok Hian Tan Yap Seng Chong Michael J. Meaney Peter D. Gluckman Johan G. Eriksson Neerja Karnani Variability in newborn telomere length is explained by inheritance and intrauterine environment BMC Medicine Newborn Telomere length Intrauterine exposures Inheritance Sex differences |
| title | Variability in newborn telomere length is explained by inheritance and intrauterine environment |
| title_full | Variability in newborn telomere length is explained by inheritance and intrauterine environment |
| title_fullStr | Variability in newborn telomere length is explained by inheritance and intrauterine environment |
| title_full_unstemmed | Variability in newborn telomere length is explained by inheritance and intrauterine environment |
| title_short | Variability in newborn telomere length is explained by inheritance and intrauterine environment |
| title_sort | variability in newborn telomere length is explained by inheritance and intrauterine environment |
| topic | Newborn Telomere length Intrauterine exposures Inheritance Sex differences |
| url | https://doi.org/10.1186/s12916-021-02217-9 |
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