Npj Ment Health Res. 2026 Jul 16;5(1):35. doi: 10.1038/s44184-026-00231-4.
ABSTRACT
The causal role of established risk factors for premenstrual disorders (PMDs) remains unclear. We used Mendelian randomization (MR) to assess causality for eight known-risk factors identified through a literature review. Summary statistics for these risk factors were from genome-wide association studies (GWAS) with sample size ranging from 129,017 to 1.2 million, and for PMDs from a GWAS of 72,297 participants. Findings were validated using one-sample MR in LifeGene cohort (n = 5674-5937). In two-sample MR, genetic liability to smoking initiation (OR = 1.25 (1.10-1.43)), earlier menarche (OR = 0.94 (0.89-0.98) per year), and higher BMI (OR = 1.19 (1.05-1.34) per kg/m2) were associated with PMD risk. No causal association was indicated for anemia, childhood abuse, childhood asthma, diabetes, and endometriosis. In one-sample MR, point estimates for BMI (OR = 1.10 (0.88-1.38) per kg/m²) and earlier menarche (OR = 0.98 (0.83-1.15) per year) were directionally consistent with the two-sample MR findings, but the confidence intervals included null effects. However, a null association was observed for smoking (OR = 0.94 (0.77-1.16)). The two-sample MR supports causal role of earlier menarche, higher BMI, and smoking in risk of PMDs. The lack of replication in one-sample MR highlights the need for triangulating evidence from future well-powered and methodologically comparable studies to strengthen these findings.
PMID:42463960 | DOI:10.1038/s44184-026-00231-4
