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A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
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Differential associations of depression-related phenotypes with cardiometabolic risks: Polygenic analyses and

Brian Chi-Fung Wong1, Carlos Kwan-Long Chau1, Fu-Kiu Ao1

  • 1School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.

Depression and Anxiety
|December 7, 2018
PubMed

Insights

This study reveals shared genetic links between depression and cardiometabolic diseases, with risks varying by depression subtype. These findings may guide targeted prevention and drug discovery for these common comorbidities.

Area of Science:

  • Genetics
  • Psychiatry
  • Cardiology

Background:

  • Depression and cardiometabolic (CM) diseases frequently co-occur, but the underlying mechanisms remain unclear.
  • The relationship between depression subtypes and CM diseases requires further investigation.

Purpose of the Study:

  • To investigate the genetic overlap between depression phenotypes and 20 CM traits.
  • To identify shared genetic variants, pathways, and potential drug repositioning opportunities for depression-CM comorbidities.

Main Methods:

  • Utilized polygenic risk scores (PRS) and LD score regression to analyze genetic overlap.
  • Included GWAS data for major depressive disorder (MDD), general depressive symptoms (DS), and neuroticism.
  • Identified shared genetic variants, enriched pathways, and potential drug candidates.

Main Results:

  • Significant genetic overlap was found between depression phenotypes (MDD, DS, neuroticism) and CM traits.
  • Most depression subtypes showed positive polygenic associations with CM abnormalities, except for MDD-CONVERGE (severe melancholic depression), which showed reduced CM risks.
  • Enrichment analyses identified inflammation-related pathways, and potential drug repositioning candidates like bupropion were highlighted.

Conclusions:

  • Shared genetic factors contribute to the comorbidity of depression and CM diseases.
  • The association between depression and CM traits varies by depression subtype, impacting cardiovascular event prevention strategies.
  • Identifying shared genetic factors can inform novel therapeutic strategies for these comorbidities.
Abstract

Keywords:
biological markerscardiovascular/cardiac/heart diseasedepressionepidemiologygenetics

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