| Application: | 42857, Influence of plasma lipoprotein genetics on infectious disease outcomes |
| Title: | Causal Inference for Genetically Determined Levels of High-Density Lipoprotein Cholesterol and Risk of Infectious Disease |
| Size: | 13.7 MB |
| Archived: | 16 Mar 2020 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
Return 2142
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Notes
Low levels of blood cholesterol are known to be associated with increased risk of infectious disease. However, it remains unclear if this relationship is causal in nature. This study assessed the influence of common variants associated with blood lipid levels on infectious disease risk in individuals of British Caucasian ancestry from the UK Biobank. Using genetic variants as risk factors can circumvent many issues of confounding and reverse causation and has the potential to provide causal inference regarding the effect of genetically determined lipid levels on susceptibility to infectious disease. Elevated levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observationally associated with reduced risk of infectious disease hospitalizations. For genetically determined lipid levels, only high-density lipoprotein cholesterol was significantly associated with reduced risk of hospitalizations for infectious disease, lower odds of outpatient antibiotic usage, and reduced risk of mortality from sepsis. Mendelian randomization analysis suggested that the observational relationship between higher levels of high-density lipoprotein cholesterol and reduced risk of hospitalization for infectious disease could be causal in nature. Our results provide causal inference for an inverse relationship between high-density lipoprotein cholesterol, but not low-density lipoprotein-cholesterol or triglycerides, and risk of an infectious hospitalization.Application 42857
Influence of plasma lipoprotein genetics on infectious disease outcomes
Lipoproteins are commonly known as "good" and "bad" cholesterol. The function of lipoproteins is to transport lipids in the blood. But lipoproteins can also bind and remove bacterial toxins from the blood during an infection and reduce the severity of disease. Therefore, it is not surprising that patients with low levels of lipoproteins have an increased risk of developing infections responsible for life-threatening hospitalization and death. Genetics influence the levels of lipoproteins in the blood, but it is unknown how these genes influence risk of infection. This study will use a large clinical database to investigate how genes that effect lipoproteins influence infectious disease risk. We predict that patients with genetic variations that enhance the ability of lipoproteins to remove bacterial toxins will have reduced risk of developing severe infections. In contrast, patients with genetic variations that impair the ability of lipoproteins to remove bacterial toxins will have increased risk of developing severe infections. This study will take 1-2 years to complete and has important public health implications. Our work will provide new information on the role of lipoprotein genetics in health and disease. By demonstrating genetic contributions to infection risk, this work has the potential to highlight the use of currently available drugs for the new purpose of treating severe infections. Furthermore, this study could help identify patients that are increased risk of developing future infections or most likely to benefit from personalized treatments given their genetics.
| Lead investigator: | Mr Mark Trinder |
| Lead institution: | University of British Columbia |
2 related Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 3248 | 42857 | Ascertainment Bias in the Association Between Elevated Lipoprotein(a) and Familial Hypercholesterolemia | 19 Mar 2021 |
| 2381 | 42857 | Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease | 3 Sep 2020 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2143 | Causal Inference for Genetically Determined Levels of High-Density Lipoprotein Cholesterol and Risk of Infectious Disease | Trinder M et al. | 2020 | Arterioscler Thromb Vasc Biol |
Enabling scientific discoveries that improve human health