Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations
Nature Genetics volume 50, pages 1219–1224 (2018)
Amit V. Khera, Mark Chaffin, Krishna G. Aragam, Mary E. Haas, Carolina Roselli, Seung Hoan Choi, Pradeep Natarajan, Eric S. Lander, Steven A. Lubitz, Patrick T. Ellinor & Sekar Kathiresan
|Disease||% of individuals|
|Type 2 diabetes||3.5|
|Inflammatory bowel disease||3.2|
|Any of the five diseases||19.8|
Cardiovascular category starts with the following
- Overview Cardiovascular and vitamin D
- Hypertension and vitamin D
- Overview Metabolic Syndrome and vitamin D
- Overview Stroke and vitamin D
- Heart Attack 647 items as of May 2018
- Arrhythmia OR “atrial fibrillation” 497 items as of May 2018
- (Arrhythmia OR “atrial fibrillation”) AND Magnesium 345 items as of May 2018
- "C-Reactive Protein" 1530 items as of June 2019
- TRIGLYCERIDES 863 items as of May 2018
- "Peripheral Artery Disease" 81 items as of Oct 2017
- "Sudden Cardiac Arrest" 98 items as of May 2018
- Search VitaminDWiki for CHF or "HEART FAILURE" 1220 items as of Aug 2017
- Search VitaminDWiki for Atherosclerosis 726 items as of Oct 2017
- Cholesterol is needed to produce both Vitamin D and Cortisol
- Overview Cholesterol and vitamin D
- Statins and vitamin D statins often reduce levels of vitamin D
- Polygenic score Wikipedia
- Why Do Polygenic Risk Scores Get So Much Hype? Aug 2018 reporting on the study on this page
"... explains the significance of using a PRS like this, “Whilst it is true that the overall predictive power for any given disease is modest—for many people with ‘average risk,’ quantifying the exact degree of genetic risk is not likely to be particularly useful—recent thinking has switched to the value of the PRS approach to pick out individuals who have particularly high or low genetic risk.” He adds that, “as this paper shows, many of these individuals have lifetime risk of disease arising from the joint action of many variants of individually small effects, that approaches that of individuals from monogenic forms of disease. It demonstrates that the former group of high-risk individuals are likely to be much more numerous than the latter."
"However, some experts are not convinced that the paper's media coverage matched the importance of the results. Ali Torkamani, Ph.D., director of genomics and genome informatics at the Scripps Research Translational Institute, told GEN that the study published last week in Nature Genetics is “not particularly” a big leap forward in the field of polygenic risk prediction. He adds that the aforementioned paper was “not a methodological advance or even an unexpected result.” Dr. McCarthy agrees that the data were not surprising and that his own group has generated similar data for T2D in their analysis of the UKBB data."
"Dr. Florez explains that, in the field of cardiac disease, PRS may be a better risk assessment tool than cholesterol measurement. If the PRS can be obtained early enough, a person could avoid the damage caused by exposure to high LDL cholesterol long before it manifests itself in the blood. "
Has a link to a web application which uses 23andme data to assess risk based on both Polygenic Score and Lifestyle - see following image
A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation 1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature 2,3,4,5, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases.
The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively.
For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk 6. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.
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