| Application: | 7089, Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank |
| Title: | Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease. |
| Size: | 196148 B |
| Archived: | 2 Aug 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 3723
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Notes
Question Does measurement of lipoprotein(a) and/or LPA genetic risk score (GRS) have clinical utility in risk prediction of incident atherosclerotic cardiovascular disease (ASCVD)?Findings In this cohort of 283 540 adults recruited by the UK Biobank, both measured lipoprotein(a) and LPA GRS were associated with comparable risk of incident ASCVD events. The LPA GRS did not yield additional prognostic information beyond measured lipoprotein(a), and both measured lipoprotein(a) and LPA GRS yielded modest improvements in the discrimination of ASCVD risk relative to the Pooled Cohort Equations or QRISK3.
Meaning Cardiovascular risk assessment with lipoprotein(a) may be achieved with either direct measurement or an LPA GRS.
Application 7089
Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank
Coronary artery disease (CAD) is the leading cause of death in the UK. When CAD occurs prematurely, the role for inheritance is greater. DNA sequencing of the protein-coding portions of the human genome ('the exome') can identify genes responsible for CAD. Here, we seek to: 1) identify all individuals in the UK Biobank with premature CAD (mean=55y, women=65y); 2) identify controls free of CAD; 3) perform whole exome sequencing on cases and controls; 4) compare sequences to discover genes responsible for CAD; 5) perform a comprehensive phenotypic scan to understand the spectrum of consequences from CAD genes. A stated purpose of UK Biobank is to improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses. We have secured funding to exome sequence up to 20,000 UK Biobank participants with and without CAD. Successful completion of this study should result in the identification of novel genetic causes for MI, the leading cause of death in the UK. Genomic variation discovered in the UK Biobank associated with MI may prove useful to target preventive strategies, understand the biology of MI in humans, and to identify novel molecular targets for therapy. We propose to: 1) identify all individuals in the UK Biobank with CAD at an early age (=55 years old in men and =65 years old in women); 2) identify controls free of CAD; 3) perform whole exome sequencing on all cases and controls; 4) compare sequences of cases with controls to discover genes responsible for CAD; and 5) understand the range of phenotypic effects from genes associated with CAD. We have secured funding to exome sequence up to 20,000 UK Biobank participants. Of note, we have secured funding to exome sequence up to 20,000 UK Biobank participants. We seek to identify all individuals in the UK Biobank with CAD at an early age (=55 years old in men and =65 years old in women). In the latest data release, there are 10,450 participants with any diagnosis code for ischemic heart disease. Further work will be required to confirm this diagnosis and restrict to CAD onset at an early age.
| Lead investigator: | Dr Pradeep Natarajan |
| Lead institution: | Broad Institute |
5 related Returns
| Return ID | App ID | Description | Archive Date |
|---|---|---|---|
| 3454 | 7089 | Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy | 26 May 2021 |
| 3725 | 7089 | Deep Learning to Predict Cardiac Magnetic Resonance-Derived Left Ventricular Mass and Hypertrophy From 12-Lead ECGs | 2 Aug 2021 |
| 3290 | 7089 | Deep learning to estimate cardiac magnetic resonance-derived left ventricular mass | 9 Apr 2021 |
| 3380 | 7089 | Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure | 26 Apr 2021 |
| 3361 | 7089 | Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions | 21 Apr 2021 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3724 | Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease | Trinder M et al. | 2020 | JAMA Cardiol |
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