Polygenic loading for major depression is associated with specific medical comorbidity

Area of Science:

• Genetics
• Psychiatry
• Cardiology

Background:

• Major depressive disorder (MDD) frequently co-occurs with medical conditions, suggesting shared genetic factors.
• Recent discovery of 15 novel genetic loci for depression enables direct investigation of this genetic overlap.
• Electronic health records (EHRs) and biobanks offer valuable data for exploring genetic associations with complex diseases.

Purpose of the Study:

• To investigate the shared genetic liability between major depressive disorder and various medical conditions.
• To examine the association between polygenic loading for depression risk loci and clinical diagnoses.
• To identify specific medical conditions that share genetic risk factors with depression.

Main Methods:

• Utilized biobank cohorts from two academic medical centers.
• Calculated polygenic loading for 15 known depression risk loci.
• Applied latent Dirichlet allocation (LDA) to group 50 clinical diagnosis topics from EHRs.
• Examined associations between depression polygenic loading and the identified diagnosis topics.

Main Results:

• Three diagnostic topics showed significant association with depression liability score.
• Associated topics included mood and anxiety disorders, cardiac ischemia, and heart failure.
• Associations with cardiac ischemia and heart failure remained significant even in individuals without mood disorder diagnoses.

Conclusions:

• Shared genetic risk exists between depression and cardiac disease.
• Genetic liability for depression is associated with increased risk of cardiac ischemia.
• Genetic liability for depression is associated with decreased risk of heart failure.