| Application: | 42857, Influence of plasma lipoprotein genetics on infectious disease outcomes |
| Title: | Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease |
| Size: | 11.6 MB |
| Archived: | 3 Sep 2020 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
Return 2381
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Notes
This study sough to answer whether the risk of atherosclerotic cardiovascular disease was different between individuals with without genetic causes for high levels of low-density lipoprotein cholesterol in the blood, termed hypercholesterolemia. In this cohort study of 48 741 adults recruited by the UK Biobank, a monogenic cause for hypercholesterolemia was found in 277 participants (0.57%) and a polygenic cause in 2379 participants (4.9%). Both polygenic and monogenic causes of hypercholesterolemia appeared to be associated with an increased risk of atherosclerotic cardiovascular disease compared with hypercholesterolemia from an unknown cause; however, monogenic hypercholesterolemia was associated with the greatest risk of atherosclerotic cardiovascular disease (need for revascularization, myocardial infarction, stroke or all-cause mortality). The findings of this study suggest that among individuals with comparable levels of low-density lipoprotein cholesterol, monogenic hypercholesterolemia may be associated with the greatest risk of atherosclerotic cardiovascular disease followed by polygenic hypercholesterolemia. Thus, understanding the possible genetic cause of hypercholesterolemia may provide important information to diagnose and treat patients with hypercholesterolemia.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 |
| 2142 | 42857 | Causal Inference for Genetically Determined Levels of High-Density Lipoprotein Cholesterol and Risk of Infectious Disease | 16 Mar 2020 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2382 | Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease | Trinder M et al. | 2020 | JAMA Cardiol |
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