Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov;290(5):980-992.
doi: 10.1111/joim.13362. Epub 2021 Aug 23.

Genetics of coronary artery disease in the post-GWAS era

Zhifen Chen  1   2 , Heribert Schunkert  1   2
Affiliations
Free article
Review

Genetics of coronary artery disease in the post-GWAS era

Zhifen Chen et al. J Intern Med. 2021 Nov.
Free article

Abstract

During the past decade, genome-wide association studies (GWAS) have transformed our understanding of many heritable traits. Three recent large-scale GWAS meta-analyses now further markedly expand the knowledge on coronary artery disease (CAD) genetics in doubling the number of loci with genome-wide significant signals. Here, we review the unprecedented discoveries of CAD GWAS on low-frequency variants, underrepresented populations, sex differences and integrated polygenic risk. We present the milestones of CAD GWAS and post-GWAS studies from 2007 to 2021, and the trend in identification of variants with smaller odds ratio by year due to the increasing sample size. We compile the 321 CAD loci discovered thus far and classify candidate genes as well as distinct functional pathways on the road to indepth biological investigation and identification of novel treatment targets. We draw attention to systems genetics in integrating these loci into gene regulatory networks within and across tissues. We review the traits, biomarkers and diseases scrutinized by Mendelian randomization studies for CAD. Finally, we discuss the potentials and concerns of polygenic scores in predicting CAD risk in patient care as well as future directions of GWAS and post-GWAS studies in the field of precision medicine.

Keywords: Mendelian randomization; coronary artery disease; genome-wide association study; polygenic risk score; precision medicine; systems genetics.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982-3021.
    1. Erdmann J, Kessler T, Munoz Venegas L, Schunkert H. A decade of genome-wide association studies for coronary artery disease: the challenges ahead. Cardiovasc Res. 2018;114(9):1241-57.
    1. Koyama S, Ito K, Terao C, Akiyama M, Horikoshi M, Momozawa Y, et al. Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease. Nat Genet. 2020;52(11):1169-77.
    1. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443-53.
    1. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316(5830):1491-3.

Publication types

LinkOut - more resources