Genetically predicted higher HDL levels are protective against most circulatory and digestive diseases but increase the risk of breast cancer and intracerebral hemorrhage.
Do genetically predicted higher HDL levels alter the risk of a wide spectrum of disease outcomes?
Genetically predicted higher HDL levels have highly disease-specific effects, offering protection against circulatory diseases while increasing the risk of certain conditions like intracerebral hemorrhage and breast cancer.
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High-density lipoprotein nHDL) is a highly heterogeneous lipoprotein with multiple physiological functions. However, observational studies present conflicting evidence regarding its association with various diseases. This study systematically summarizes evidence from Mendelian randomization (MR) studies to investigate the causal relationships between HDL-related biomarkers and a wide spectrum of disease outcomes. We systematically searched multiple databases up to November 2024. The causal relationship between HDL and 158 diseases was studied. Findings reveal that the role of HDL is highly disease-specific. Genetically predicted higher HDL levels are protective against the majority of circulatory and digestive system diseases. Conversely, they are associated with an increased risk of certain conditions, including breast cancer, intracerebral hemorrhage, and age-related macular degeneration. MR analyses revealed inconsistent and sometimes conflicting findings for several disease outcomes, notably including Alzheimer's disease. This review underscores the context-dependent nature of HDL's effects, which may be driven by factors like HDL particle heterogeneity and functional transformation into a pro-inflammatory state. Future research should move beyond concentration-based metrics to focus on HDL functionality and precise subtyping to fully understand its role in disease etiology.
Wu et al. (Thu,) reported a other. Genetically predicted higher HDL levels are protective against most circulatory and digestive diseases but increase the risk of breast cancer and intracerebral hemorrhage.