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Body Mass Index and Polycystic Ovary Syndrome: A Two-sample Bidirectional Mendelian Randomization Study.

BACKGROUND
Observational studies have shown a link between elevated body mass index (BMI) and the risk of polycystic ovary syndrome (PCOS). While Mendelian randomization (MR) studies in Europeans have suggested a causal role of increased BMI in PCOS, whether the same role is suggested in Asians has yet to be investigated. We used MR studies to infer causal effects using genetic data from East Asian populations.


METHODS AND FINDINGS
We performed a two-sample bidirectional MR using summary statistics from genome-wide association studies (GWAS) of BMI (with up to 173,430 individuals) and PCOS (4,386 cases and 8,017 controls) in East Asian populations. Seventy-eight single nucleotide polymorphisms (SNPs) correlated with BMI were selected as genetic instrumental variables to estimate the causal effect of BMI on PCOS using the inverse-variance weighted (IVW) method. To test the reliability of the results, further sensitivity analyses included MR-Egger regression, weighted median estimates, and leave-one-out analysis. The IVW analysis indicated a significant association between high BMI and the risk of PCOS (odds ratio (OR) per-SD higher BMI, 2.208; 95% Confidence interval (CI) 1.537 to 3.168, P=1.77×10-5). In contrast, the genetic risk of PCOS had no significant effect on BMI.


CONCLUSIONS
The results of our bidirectional MR study showed that an increase in BMI causes PCOS, while PCOS does not cause an increased BMI. This study provides further genetic support for a link between BMI and PCOS. Further research is needed to interpret the potential mechanisms of this association.