TY - JOUR
T1 - Assessing causality between childhood adiposity and early puberty
T2 - A bidirectional Mendelian randomization and longitudinal study
AU - Chen, Yang Ching
AU - Fan, Hsien Yu
AU - Yang, Chen
AU - Hsieh, Rong Hong
AU - Pan, Wen Harn
AU - Lee, Yungling L.
N1 - Funding Information:
This study was supported by a grant from the National Health Research Institutes of Taiwan ( NHRI-EX107-10718PC and NHRI-EX107-10606PI ); 106-2314-B-002-131-MY3 and 107-2314-B-532-002-MY3 from Ministry of Science and Technology of Taiwan and UN107-002 from National Taiwan University Hospital .
Funding Information:
The authors thank the field workers, teachers, and other school staff who supported the data collection, as well as all the parents and children who participated in this study. We also thank the NCGM for the genotyping technical support. This study was supported by a grant from the National Health Research Institutes of Taiwan (NHRI-EX107-10718PC and NHRI-EX107-10606PI); 106-2314-B-002-131-MY3 and 107-2314-B-532-002-MY3 from Ministry of Science and Technology of Taiwan and UN107-002 from National Taiwan University Hospital. The authors have no conflicts of interest relevant to this article to disclose. Dr. Yang-Ching Chen contributed to the conceptualization and design the study, the cohort data collection, interpretation of data, and writing. Mr. Hsien-Yu Fan assisted in the critical part of the statistical analysis, interpreted data, and revised the manuscript critically for important intellectual content. Dr. Chen Yang contributed to hypothesis generation, interpreted data, and revised the draft of the manuscript. Prof. Rong-Hong Hsieh contributed to the analysis and interpretation of data and critically revised the manuscript for intellectual content. Prof. Wen-Harn Pan critically reviewed the revised manuscript. Prof. Yungling Lee reviewed the study design, acquired and interpreted data, supervised the study, and revised the manuscript critically for valuable intellectual content. All authors approved the final manuscript for submission and publication and agree to be accountable for all aspects of the work. All authors agreed to the terms of the copyright transfer/affirmation of originality, and provide the appropriate disclosure of potential conflicts of interest.? Disclosure summary: The authors have no financial relationships relevant to this article to disclose.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Aims: Obesity and early puberty have been reported to be mutually causative. We investigated the causal relationship between adiposity and early puberty by performing bidirectional Mendelian randomization (MR) and longitudinal data analyses. Methods: We used information from the Taiwan Children Health Study (3109 adolescents aged 11–12 years) with 17 body mass index (BMI)- and 10 puberty-related single-nucleotide polymorphisms (SNPs) to produce genetic instrumental variables (IVs). The two-stage least squares (2SLS) method, MR sensitivity analysis, and survival analysis were used to explore and confirm causality. Results: Regression estimates from IVs revealed that significantly increased association of BMI with early puberty was noted (coefficients: 0.13, 0.10, and 0.09; 95% CI: 0.07–0.19, 0.02–0.19, and 0.02–0.16 for all participants, male adolescents, and female adolescents, respectively). Genetic IVs for puberty were not associated with BMI. MR sensitivity and two-sample MR analyses produced similar results. Longitudinal analysis results revealed that prepubertal overweight and obesity could predict early onset of puberty. However, after excluding children with a history of overweight and obesity at the age of 7–12 years, early puberty was not found to trigger new-onset of overweight and obesity at the age of 18 years in either sex. Conclusions: Higher adiposity may lead to early puberty. However, the causal effects of early puberty on adiposity accumulation were not supported by our data. Targeted interventions to reduce childhood obesity are strongly recommended to prevent obesity-related comorbidities, as well as early puberty onset.
AB - Aims: Obesity and early puberty have been reported to be mutually causative. We investigated the causal relationship between adiposity and early puberty by performing bidirectional Mendelian randomization (MR) and longitudinal data analyses. Methods: We used information from the Taiwan Children Health Study (3109 adolescents aged 11–12 years) with 17 body mass index (BMI)- and 10 puberty-related single-nucleotide polymorphisms (SNPs) to produce genetic instrumental variables (IVs). The two-stage least squares (2SLS) method, MR sensitivity analysis, and survival analysis were used to explore and confirm causality. Results: Regression estimates from IVs revealed that significantly increased association of BMI with early puberty was noted (coefficients: 0.13, 0.10, and 0.09; 95% CI: 0.07–0.19, 0.02–0.19, and 0.02–0.16 for all participants, male adolescents, and female adolescents, respectively). Genetic IVs for puberty were not associated with BMI. MR sensitivity and two-sample MR analyses produced similar results. Longitudinal analysis results revealed that prepubertal overweight and obesity could predict early onset of puberty. However, after excluding children with a history of overweight and obesity at the age of 7–12 years, early puberty was not found to trigger new-onset of overweight and obesity at the age of 18 years in either sex. Conclusions: Higher adiposity may lead to early puberty. However, the causal effects of early puberty on adiposity accumulation were not supported by our data. Targeted interventions to reduce childhood obesity are strongly recommended to prevent obesity-related comorbidities, as well as early puberty onset.
KW - Causality
KW - Early puberty
KW - Longitudinal study
KW - Mendelian randomization analysis
KW - Overweight
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U2 - 10.1016/j.metabol.2019.153961
DO - 10.1016/j.metabol.2019.153961
M3 - Article
AN - SCOPUS:85071014406
SN - 0026-0495
VL - 100
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
M1 - 153961
ER -
