Genomic risk prediction of coronary artery disease in nearly 500,000 adults: implications for early screening and primary prevention
By
Michael Inouye,
Gad Abraham,
Christopher P Nelson,
Angela M. Wood,
Michael J Sweeting,
Frank Dudbridge,
Florence Y Lai,
Stephen Kaptoge,
Marta Brozynska,
Tingting Wang,
Shu Ye,
Thomas R. Webb,
Martin K Rutter,
Ioanna Tzoulaki,
Riyaz S Patel,
Ruth J.F. Loos,
Bernard Keavney,
Harry Hemingway,
John Thompson,
Hugh Watkins,
Panos Deloukas,
Emanuele Di Angelantonio,
Adam S. Butterworth,
John Danesh,
Nilesh J. Samani,
for The UK Biobank CardioMetabolic Consortium CHD Working Group
Posted 19 Jan 2018
bioRxiv DOI: 10.1101/250712
Background: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture; however, genomic risk scores have not yet leveraged the totality of genetic information available nor been externally tested at population-scale to show potential utility in primary prevention. Methods: Using a meta-analytic approach to combine large-scale genome-wide and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS), consisting of 1.7 million genetic variants. We externally tested metaGRS, individually and in combination with available conventional risk factors, in 22,242 CAD cases and 460,387 non-cases from UK Biobank. Findings: In UK Biobank, a standard deviation increase in metaGRS had a hazard ratio (HR) of 1.71 (95% CI 1.68-1.73) for CAD, greater than any other externally tested genetic risk score. Individuals in the top 20% of the metaGRS distribution had a HR of 4.17 (95% CI 3.97-4.38) compared with those in the bottom 20%. The metaGRS had higher C-index (C=0.623, 95% CI 0.615-0.631) for incident CAD than any of four conventional factors (smoking, diabetes, hypertension, and body mass index), and addition of the metaGRS to a model of conventional risk factors increased C-index by 3.7%. In individuals on lipid-lowering or anti-hypertensive medications at recruitment, metaGRS hazard for incident CAD was significantly but only partially attenuated with HR of 2.83 (95% CI 2.61-3.07) between the top and bottom 20% of the metaGRS distribution. Interpretation: Recent genetic association studies have yielded enough information to meaningfully stratify individuals using the metaGRS for CAD risk in both early and later life, thus enabling targeted primary intervention in combination with conventional risk factors. The metaGRS effect was partially attenuated by lipid and blood pressure-lowering medication, however other prevention strategies will be required to fully benefit from earlier genomic risk stratification.
Download data
- Downloaded 3,989 times
- Download rankings, all-time:
- Site-wide: 2,198 out of 119,003
- In genetics: 96 out of 5,150
- Year to date:
- Site-wide: 29,987 out of 119,003
- Since beginning of last month:
- Site-wide: 9,951 out of 119,003
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!