Genetic overlap and causality between depression and preterm birth: a large-scale genome-wide cross-trait analysis

Area of Science:

• Psychiatric Genetics
• Reproductive Health
• Genomics

Background:

• The shared genetic basis between depression and preterm birth (PTB) remains largely unexplored.
• Understanding this genetic overlap is crucial for identifying common biological pathways.

Purpose of the Study:

• To investigate the genetic overlap and causality between depression and PTB.
• To identify shared genetic loci and potential causal relationships.

Main Methods:

• Genome-wide cross-trait analysis using summary statistics from large-scale GWAS for depression and PTB.
• Linkage disequilibrium score regression and genetic covariance analysis for genetic correlations.
• Mendelian randomization to infer causal relationships.

Main Results:

• Significant positive genetic correlations were found between PTB and broad depression (r_g=0.242), major depression (r_g=0.236), and bipolar disorder (r_g=0.133).
• Shared genetic loci were identified, including novel loci rs7813444, rs3132948, and rs9273363.
• Genetic liability to broad and major depression significantly increased PTB risk (OR=1.30 and OR=1.27, respectively).

Conclusions:

• An intrinsic genetic link exists between depression and PTB.
• Findings highlight the importance of depression screening and intervention for PTB prevention.
• Potential for novel therapeutic strategies targeting shared biological mechanisms.