Phenome-wide Mendelian Randomization of Triglycerides and 2600 Diseases

What is it about?

The study conducted a phenome-wide, two-sample Mendelian randomization (MR) analysis to investigate the causal effects of plasma triglyceride (TG) levels on 2600 disease traits in the European ancestry population of UK Biobank. The results identified seven disease traits reaching Bonferroni-corrected significance in both the discovery and replication analyses, suggesting a causal relationship between plasma TG levels and ASCVDs. The study also identified 12 disease traits that were Bonferroni-significant in the discovery or replication analysis and at least nominally significant in the other analysis, identifying plasma TG levels as a novel potential risk factor for nine non-ASCVD diseases.

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Why is it important?

This study is important because it provides new insights into the causal relationship between plasma triglyceride (TG) levels and various diseases, including both ASCVDs and non-ASCVDs. By using a phenome-wide, two-sample Mendelian randomization approach, the research identifies novel potential risk factors and drug repurposing opportunities, as well as mechanistic insights for future studies. Key Takeaways: 1. The study identifies seven disease traits with a causal relationship between plasma TG levels and ASCVDs. 2. Plasma TG levels are positively associated with uterine leiomyoma, highlighting a potential novel risk factor for the disease. 3. The study identifies several non-ASCVD diseases with a potential causal relationship with plasma TG levels, suggesting new opportunities for drug repurposing and experimental studies. 4. The study emphasizes the importance of accounting for correlated lipid fractions to distinguish the independent effect of plasma TG levels on disease risk. 5. The findings suggest that plasma TG measurement captures a clinically significant mechanism associated with ASCVD risk, which may be mediated by the concentration of ApoB particles in TRLs.