Genetic Analysis Confirms Two-Way Link Between BMI and PCOS

TOPLINE:

Elevated body mass index (BMI) is associated with an increased risk for polycystic ovarian syndrome (PCOS); conversely, the severity of PCOS may contribute to a higher BMI.

METHODOLOGY:

• Women with obesity and PCOS have difficulty conceiving naturally, suggesting that BMI affects fertility in these patients.
• To explore causality between BMI and PCOS, researchers used a bidirectional, two-sample Mendelian randomization (MR) approach with genome-wide association studies (GWAS) summary data from two large independent European populations: The UK Biobank for BMI and the FinnGen biobank for PCOS.
• They applied three analytical methods: Inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression.
• Overall, the analysis included 427 single-nucleotide polymorphisms (SNPs) associated with BMI and 169 SNPs associated with PCOS.

TAKEAWAY:

• Researchers found a positive association between increased BMI and a higher risk for PCOS across all methods used (IVW: odds ratio [OR], 2.027; weighted median estimator: OR, 2.368; MR-Egger regression: OR, 3.610; P < .001 for all).
• Genetic predisposition to PCOS had a causal effect on elevated BMI (IVW: OR, 1.020; weighted median estimator: OR, 1.017; P < .001 for both).

IN PRACTICE:

“The findings highlight the importance of recognizing and safeguarding populations at risk of PCOS due to overweight or obesity,” the authors wrote. “Inversely, our research found that the severity of PCOS may also be one of the potential factors contributing to BMI increase, possibly informing innovative prevention and treatment strategies,” they added.

SOURCE:

The study, led by Yifan Fang, Fujian Children’s Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

Use of data from a European population may have limited the generalizability of findings to a broader population. There was significant heterogeneity among the genetic instruments used in GWAS. There was a possibility of overestimation of the SNP-exposure association. Furthermore, limited PCOS cases may have reduced statistical power of the MR analysis.

DISCLOSURES:

The study was supported by The Natural Science Foundation of Fujian Province and The Foundation of Fujian High-level Clinical Medical Center. The authors declared no conflicts of interest.