Causal relationships between birth weight, childhood obesity and age at menarche: A two-sample Mendelian randomization analysis.

OBJECTIVES

Observational studies suggest birth weight and childhood obesity are closely associated with age at menarche. However, the relationships between them are currently inconsistent and it remains elusive whether such associations are causal. Therefore, the aim of the study was to investigate whether there existed causal relationships between birth weight, childhood obesity and age at menarche.

DESIGN, PATIENTS AND MEASUREMENTS: A two-sample Mendelian randomization (MR) study. The standard inverse variance weighted MR analyses were adopted to evaluate the causal effects of birth weight (n = 143,677), childhood body mass index (BMI) (n = 39,620) on age at menarche (n = 182,416) with summary statistics from large-scale genome-wide association studies (GWASs). Meanwhile, we validated our MR results with some sensitivity analyses including maximum likelihood, weighted-median and MR pleiotropy residual sum and outlier methods.

RESULTS

The present study showed that each one standard deviation (1-SD) lower birth weight was predicted to result in a 0.1479 years earlier of age at menarche (β = .1479, 95% confidence interval [CI] = 0.0422-0.2535; p = 0.0061). We also found that genetically predicted 1-SD increase in childhood BMI was causally associated with early age at menarche (β = -.3966, 95% CI = -0.5294 to -0.2639; p = 4.73E-09).

CONCLUSIONS

Our MR study suggests the causal effect of lower birth weight and higher childhood BMI on the increased risk of earlier menarche. It may be the opportune time to carry out weight control intervention in prenatal and early childhood development periods to prevent early menarche onset, thus decreasing the future adverse consequences.