Women's reproductive traits and major depressive disorder: A two-sample Mendelian randomization study

Area of Science:

• Reproductive health
• Psychiatry
• Genetics

Background:

• Strong associations exist between women's reproductive factors and major depressive disorder (MDD).
• The causal relationship between these factors and MDD remains unclear.

Purpose of the Study:

• To investigate the causal effects of women's reproductive traits on MDD using Mendelian randomization (MR).

Main Methods:

• Employed two-sample univariable and multivariable Mendelian randomization (MR) analyses.
• Utilized female-specific single nucleotide polymorphisms (SNPs) from large-scale genome-wide association studies.
• Conducted sensitivity analyses including MR-Egger, weighted median, and GSMR.

Main Results:

• Genetically predicted later age at menarche (AAM), age at first birth (AFB), and age at first sexual intercourse (AFS) were associated with lower MDD risk.
• Multivariable MR confirmed significant causal effects of earlier AAM, AFB, and AFS on increased MDD risk after adjusting for BMI and educational attainment.

Conclusions:

• Early AAM, AFB, and AFS are identified as risk factors for MDD.
• Enhancing awareness of reproductive health care for women may contribute to reducing MDD incidence.