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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U2 - 10.1016/j.orcp.2018.07.008
DO - 10.1016/j.orcp.2018.07.008
M3 - Article
AN - SCOPUS:85050863420
JO - Obesity Research and Clinical Practice
JF - Obesity Research and Clinical Practice
SN - 1871-403X
ER -