Association of birth weight, childhood obesity, and age at menarche with the risk of ovarian dysfunction: A mendelian randomization study

• Published in: PloS one 2024-07, Vol.19 (7), p.e0306365
• Main Authors: Dang, Chunxiao, Li, Jianjuan, Yu, Xiao, Liu, Jinxing, Liu, Pengfei, Yang, Xiaoling
• Format: Article
• Language: English
• Subjects: Adolescent; Age; Age Factors; Biology and Life Sciences; Birth weight; Birth Weight - genetics; Child; Childhood; Children; Confounding (Statistics); Consortia; Eggs; Female; Genetic diversity; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Heterogeneity; Humans; Impact analysis; Medicine and Health Sciences; Menarche; Menarche - genetics; Mendelian Randomization Analysis; Obesity; Obesity in children; Observational studies; Ovaries; Pediatric Obesity - epidemiology; Pediatric Obesity - genetics; Physical Sciences; Pleiotropy; Population genetics; Population studies; Randomization; Research and Analysis Methods; Risk analysis; Risk Factors; Risk management; Risk reduction; Sensitivity analysis; Variables; Variance analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0306365

Observational studies have revealed associations between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. However, these studies are susceptible to unavoidable confounding factors, leading to ongoing debates regarding their conclusions and making causal relationships challenging to infer. In light of these challenges, Mendelian randomization was employed in this study to investigate the causal relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. This study employed a two-sample Mendelian randomization approach using genetic variation as instrumental variables to investigate causal relationships. Genetic variation data were sourced from summary data of genome-wide association studies in European populations. Instrumental variables were selected based on the principles of Mendel's three assumptions. The study utilized the inverse variance weighted method to assess the relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, and the weighted median mode to complement the IVW results. Furthermore, the study conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to evaluate the robustness of the results. Based on the inverse variance weighted method, it was found that there exists a causal relationship between childhood obesity (OR = 1.378, 95% CI: 1.113∼1.705, p = 0.003), age at menarche (OR = 0.639, 95% CI: 0.468∼0.871, p = 0.005), and ovarian dysfunction, while no causal relationship was observed between birth weight and ovarian dysfunction. Heterogeneity tests, multiplicity tests, and leave-one-out sensitivity analyses did not detect any heterogeneity or multiplicity effects in the estimated impact of these three exposure factors on the risk of ovarian dysfunction. This study represents the first evidence suggesting a potential causal relationship between childhood obesity, age at menarche, and ovarian dysfunction. Childhood obesity was found to increase the risk of ovarian dysfunction, while a later age at menarche was associated with a reduced risk of ovarian dysfunction.