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Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases

Fuquan Zhang1,2,3, Hongbao Cao4, Ancha Baranova4,5

  • 1Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China.

Frontiers in Cardiovascular Medicine
|December 3, 2021
PubMed

Insights

Genetic links between major depressive disorder (MDD) and cardiovascular diseases (CVD) are substantial. Shared genetic factors indicate that MDD may increase the risk for stroke and coronary artery disease (CAD).

Area of Science:

  • Genetics
  • Psychiatry
  • Cardiology

Background:

  • Major depressive disorder (MDD) is frequently observed alongside cardiovascular diseases (CVD).
  • The underlying biological mechanisms connecting MDD and CVD require further investigation.
  • Shared genetic variations are hypothesized to play a role in this association.

Purpose of the Study:

  • To investigate the shared genetic architecture between MDD and various cardiovascular outcomes.
  • To identify causal relationships between MDD and cardiovascular traits using genetic data.
  • To pinpoint specific genes and genomic regions implicated in both MDD and CVD.

Main Methods:

  • Polygenic overlap analysis to assess genetic correlation between MDD and seven cardiovascular outcomes (CAD, heart failure, atrial fibrillation, stroke, systolic blood pressure, diastolic blood pressure, pulse pressure).
  • Mendelian randomization analysis to infer causal effects of MDD on cardiovascular traits.
  • Cross-trait meta-analysis and transcriptome-wide association fine-mapping to identify shared genomic loci and prioritize causal genes.

Main Results:

  • Significant genetic overlap was detected between MDD and CVD, particularly with stroke and coronary artery disease (CAD).
  • Mendelian randomization suggested a causal effect of genetic liability to MDD on the risk of CAD and stroke.
  • A specific pleiotropic region at 20q12 was identified as conferring risk for both MDD and CVD.
  • Novel risk genes for MDD and stroke, including RPL31P12, BORSC7, PNPT11, and PGF, were identified through cross-trait analyses.

Conclusions:

  • Genetic liability to major depressive disorder is associated with an increased risk for cardiovascular diseases, including stroke and CAD.
  • Shared genetic variations contribute significantly to the co-occurrence of MDD and CVD.
  • The findings elucidate mechanistic links between mental health and cardiovascular health at a genetic level.

Keywords:
Mendelian randomizationcardiovascular diseasemajor depressive disorderpolygenic overlapstroke

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