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Assessing causality between childhood adiposity and early puberty: A bidirectional Mendelian randomization and longitudinal study.
Metabolism ( IF 10.8 ) Pub Date : 2019-08-15 , DOI: 10.1016/j.metabol.2019.153961 Yang-Ching Chen , Hsien-Yu Fan , Chen Yang , Rong-Hong Hsieh , Wen-Harn Pan , Yungling L. Lee
Metabolism ( IF 10.8 ) Pub Date : 2019-08-15 , DOI: 10.1016/j.metabol.2019.153961 Yang-Ching Chen , Hsien-Yu Fan , Chen Yang , Rong-Hong Hsieh , Wen-Harn Pan , Yungling L. Lee
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.
更新日期:2019-08-15