Birthweight, time-varying adiposity growth and early menarche in girls

A Mendelian randomisation and mediation analysis

Hsien Yu Fan, Yen Tsung Huang, Rong Hong Hsieh, Jane C.J. Chao, Yi Ching Tung, Yungling L. Lee, Yang Ching Chen

Research output: Contribution to journalArticle

Abstract

Objective: To explore the causal effect of time-varying z-BMI growth on early menarche using Mendelian randomisation (MR); to identify critical adiposity predictors of early menarche; to compare the effects of birthweight and time-varying z-BMI growth as mediators of the path from genes to early menarche using mediation analysis. Methods: We used data from the Taiwan Children Health Study with 21 obesity-related single-nucleotide polymorphisms (SNPs) to yield genetic (instrumental variable)IVs for adiposity. Children with available data on genotyping, birthweight, adiposity, and menarcheal age were included. Results: In MR analyses, results based on the time-varying z-BMI growth show more statistical power and capture more information of adiposity growth (p = 0.01) than those based on single point z-BMI (p = 0.02). Among adiposity measures, critical predictors of early menarche are fat free mass (RR = 1.33, 95% CI 1.07–1.65) and waist/height ratio (RR = 1.27, 95% CI 1.03–1.56). Other potential predictors of early menarche are sum of skinfold (RR = 1.24, 95% CI 1.03–1.48) and total body fat (RR = 1.20, 95% CI 1.05–1.38). In both one-mediation and multi-mediation analyses, time-varying z-BMI growth in the prepubertal years plays a crucial mediator in the pathway from the genes to early menarche. Conclusions: This study discovered that greater prepubertal adiposity growth is a crucial mediator in the path from genes to early menarche. For girls with genes positively associated with obesity; and/or of lower birthweight, a strategy to prevent childhood adiposity should be implemented in order to avoid early menarche development.

Original languageEnglish
JournalObesity Research and Clinical Practice
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Mendelian Randomization Analysis
Menarche
Adiposity
Growth
Genes
Obesity
Random Allocation
Taiwan
Single Nucleotide Polymorphism
Adipose Tissue
Fats

Keywords

  • Adiposity growth
  • Birthweight
  • Early menarche
  • Mediation analysis
  • Mendelian randomisation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

@article{d27e429d0f2e4addb33a5048f4cb0f64,
title = "Birthweight, time-varying adiposity growth and early menarche in girls: A Mendelian randomisation and mediation analysis",
abstract = "Objective: To explore the causal effect of time-varying z-BMI growth on early menarche using Mendelian randomisation (MR); to identify critical adiposity predictors of early menarche; to compare the effects of birthweight and time-varying z-BMI growth as mediators of the path from genes to early menarche using mediation analysis. Methods: We used data from the Taiwan Children Health Study with 21 obesity-related single-nucleotide polymorphisms (SNPs) to yield genetic (instrumental variable)IVs for adiposity. Children with available data on genotyping, birthweight, adiposity, and menarcheal age were included. Results: In MR analyses, results based on the time-varying z-BMI growth show more statistical power and capture more information of adiposity growth (p = 0.01) than those based on single point z-BMI (p = 0.02). Among adiposity measures, critical predictors of early menarche are fat free mass (RR = 1.33, 95{\%} CI 1.07–1.65) and waist/height ratio (RR = 1.27, 95{\%} CI 1.03–1.56). Other potential predictors of early menarche are sum of skinfold (RR = 1.24, 95{\%} CI 1.03–1.48) and total body fat (RR = 1.20, 95{\%} CI 1.05–1.38). In both one-mediation and multi-mediation analyses, time-varying z-BMI growth in the prepubertal years plays a crucial mediator in the pathway from the genes to early menarche. Conclusions: This study discovered that greater prepubertal adiposity growth is a crucial mediator in the path from genes to early menarche. For girls with genes positively associated with obesity; and/or of lower birthweight, a strategy to prevent childhood adiposity should be implemented in order to avoid early menarche development.",
keywords = "Adiposity growth, Birthweight, Early menarche, Mediation analysis, Mendelian randomisation",
author = "Fan, {Hsien Yu} and Huang, {Yen Tsung} and Hsieh, {Rong Hong} and Chao, {Jane C.J.} and Tung, {Yi Ching} and Lee, {Yungling L.} and Chen, {Yang Ching}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.orcp.2018.07.008",
language = "English",
journal = "Obesity Research and Clinical Practice",
issn = "1871-403X",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Birthweight, time-varying adiposity growth and early menarche in girls

T2 - A Mendelian randomisation and mediation analysis

AU - Fan, Hsien Yu

AU - Huang, Yen Tsung

AU - Hsieh, Rong Hong

AU - Chao, Jane C.J.

AU - Tung, Yi Ching

AU - Lee, Yungling L.

AU - Chen, Yang Ching

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: To explore the causal effect of time-varying z-BMI growth on early menarche using Mendelian randomisation (MR); to identify critical adiposity predictors of early menarche; to compare the effects of birthweight and time-varying z-BMI growth as mediators of the path from genes to early menarche using mediation analysis. Methods: We used data from the Taiwan Children Health Study with 21 obesity-related single-nucleotide polymorphisms (SNPs) to yield genetic (instrumental variable)IVs for adiposity. Children with available data on genotyping, birthweight, adiposity, and menarcheal age were included. Results: In MR analyses, results based on the time-varying z-BMI growth show more statistical power and capture more information of adiposity growth (p = 0.01) than those based on single point z-BMI (p = 0.02). Among adiposity measures, critical predictors of early menarche are fat free mass (RR = 1.33, 95% CI 1.07–1.65) and waist/height ratio (RR = 1.27, 95% CI 1.03–1.56). Other potential predictors of early menarche are sum of skinfold (RR = 1.24, 95% CI 1.03–1.48) and total body fat (RR = 1.20, 95% CI 1.05–1.38). In both one-mediation and multi-mediation analyses, time-varying z-BMI growth in the prepubertal years plays a crucial mediator in the pathway from the genes to early menarche. Conclusions: This study discovered that greater prepubertal adiposity growth is a crucial mediator in the path from genes to early menarche. For girls with genes positively associated with obesity; and/or of lower birthweight, a strategy to prevent childhood adiposity should be implemented in order to avoid early menarche development.

AB - Objective: To explore the causal effect of time-varying z-BMI growth on early menarche using Mendelian randomisation (MR); to identify critical adiposity predictors of early menarche; to compare the effects of birthweight and time-varying z-BMI growth as mediators of the path from genes to early menarche using mediation analysis. Methods: We used data from the Taiwan Children Health Study with 21 obesity-related single-nucleotide polymorphisms (SNPs) to yield genetic (instrumental variable)IVs for adiposity. Children with available data on genotyping, birthweight, adiposity, and menarcheal age were included. Results: In MR analyses, results based on the time-varying z-BMI growth show more statistical power and capture more information of adiposity growth (p = 0.01) than those based on single point z-BMI (p = 0.02). Among adiposity measures, critical predictors of early menarche are fat free mass (RR = 1.33, 95% CI 1.07–1.65) and waist/height ratio (RR = 1.27, 95% CI 1.03–1.56). Other potential predictors of early menarche are sum of skinfold (RR = 1.24, 95% CI 1.03–1.48) and total body fat (RR = 1.20, 95% CI 1.05–1.38). In both one-mediation and multi-mediation analyses, time-varying z-BMI growth in the prepubertal years plays a crucial mediator in the pathway from the genes to early menarche. Conclusions: This study discovered that greater prepubertal adiposity growth is a crucial mediator in the path from genes to early menarche. For girls with genes positively associated with obesity; and/or of lower birthweight, a strategy to prevent childhood adiposity should be implemented in order to avoid early menarche development.

KW - Adiposity growth

KW - Birthweight

KW - Early menarche

KW - Mediation analysis

KW - Mendelian randomisation

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SN - 1871-403X

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