Assessing causality between childhood adiposity and early puberty

A bidirectional Mendelian randomization and longitudinal study

Yang Ching Chen, Hsien Yu Fan, Chen Yang, Rong Hong Hsieh, Wen Harn Pan, Yungling L. Lee

研究成果: 雜誌貢獻文章

摘要

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.

原文英語
文章編號153961
期刊Metabolism: Clinical and Experimental
100
DOIs
出版狀態已發佈 - 十一月 1 2019

指紋

Adiposity
Puberty
Random Allocation
Causality
Longitudinal Studies
Obesity
Mendelian Randomization Analysis
Body Mass Index
Pediatric Obesity
Survival Analysis
Least-Squares Analysis
Taiwan
Single Nucleotide Polymorphism
Comorbidity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

引用此文

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title = "Assessing causality between childhood adiposity and early puberty: A bidirectional Mendelian randomization and longitudinal study",
abstract = "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.",
keywords = "Causality, Early puberty, Longitudinal study, Mendelian randomization analysis, Overweight",
author = "Chen, {Yang Ching} and Fan, {Hsien Yu} and Chen Yang and Hsieh, {Rong Hong} and Pan, {Wen Harn} and Lee, {Yungling L.}",
year = "2019",
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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.

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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