Fan H.-Y.Huang Y.-T.Hsieh R.-H.Chao J.C.-J.YI-CHING TUNGLee Y.L.Chen Y.-C.2021-01-082021-01-0820181871-403Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85050863420&doi=10.1016%2fj.orcp.2018.07.008&partnerID=40&md5=58dff7f215b2a66baa14b55b31a22238https://scholars.lib.ntu.edu.tw/handle/123456789/540113Objective: 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. ? 2018 Asia Oceania Association for the Study of ObesityAdiposity growth; Birthweight; Early menarche; Mediation analysis; Mendelian randomisation[SDGs]SDG3abdominal obesity; Article; birth weight; body fat; body mass; child; cohort analysis; confidence interval; correlation analysis; early menarche; fat free mass; female; gene frequency; genetic risk; genetic variability; genotype; human; major clinical study; menarche; Mendelian randomization analysis; obesity; outcome assessment; prepuberty; priority journal; school child; sensitivity analysis; single nucleotide polymorphism; skinfold; statistical analysis; Taiwan; waist to height ratio; birth weight; childhood obesity; genetics; menarche; obesity; pathophysiology; physiology; Adiposity; Birth Weight; Body Mass Index; Child; Female; Humans; Menarche; Pediatric Obesity; Polymorphism, Single Nucleotidejournal article10.1016/j.orcp.2018.07.008300822482-s2.0-85050863420