Genetics of mood instability and risk of cardiovascular diseases: A univariable and multivariable Mendelian...

Area of Science:

• Genetics and Cardiovascular Health
• Mental Health and Disease Etiology

Background:

• Cardiovascular diseases (CVDs) are a leading cause of global mortality and disability.
• Emerging research indicates a significant link between mental health and CVD risk.
• Traditional risk factors do not fully explain CVD development, prompting investigation into other factors like mood instability.

Purpose of the Study:

• To investigate the potential causal associations between mood instability and various cardiovascular diseases (CVDs).
• To utilize Mendelian randomization (MR) analysis to explore genetic predispositions for mood instability and their impact on CVD risk.

Main Methods:

• Employed 62 single-nucleotide polymorphisms associated with mood instability as instrumental variables from the UK Biobank.
• Utilized summary-level data from genome-wide association studies for seven CVDs.
• Applied random-effects inverse-variance weighted method and conducted sensitivity analyses with various MR methods for validation.

Main Results:

• Genetic liability to mood instability showed significant associations with increased odds of six CVDs: deep vein thrombosis, pulmonary embolism, heart failure, arterial hypertension, myocardial infarction, and coronary artery disease.
• Mood instability's genetic component was also linked to higher levels of HDL cholesterol, triglycerides, body mass index, smoking, and depression.
• These associations remained independent of traditional cardiovascular risk factors in multivariable MR models.

Conclusions:

• The Mendelian randomization study suggests a potential causal relationship between genetic liability to mood instability and an elevated risk of multiple cardiovascular diseases.
• This finding underscores the importance of considering mental health, specifically mood instability, in cardiovascular disease prevention and management strategies.