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PLoS One. 2019 Feb 6;14(2):e0211690. doi: 10.1371/journal.pone.0211690. eCollection 2019.

Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations.

Author information

1
Department of Cardiology, Herlev and Gentofte Hospital, Hellerup, Denmark.
2
Unit of Epidemiology and biostatistics, Aalborg University Hospital, Aalborg, Denmark.
3
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
4
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Department of Internal Medicine, Section of Cardiology, Amager and Hvidovre Hospital Glostrup, Glostrup, Denmark.
6
Department of Cardiology, Roskilde Hospital, Roskilde, Denmark.
7
Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg, Denmark.
8
Department of Biomedicine, University of Copenhagen, Copenhagen, Denmark.
9
Department of Cardiology, Amager and Hvidovre Hospital Hvidovre, Hvidovre, Denmark.
10
Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
11
Department of Cardiology, Nephrology, and Endocrinology, Hillerød Hospital, Hillerød, Denmark.
12
Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
13
Department of Clinical Biochemistry, Copenhagen University Hospital, Gentofte, Denmark.
14
The Danish Heart Foundation, Copenhagen, Denmark.
15
The National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
16
Laboratory of Clinical Pharmacology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
17
Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.
18
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
19
Steno Diabetes Center, Gentofte, Denmark.
20
Department of Health Science and Technology, Aalborg University Hospital, Aalborg, Denmark.
21
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.

Abstract

BACKGROUND:

The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography.

METHODS:

1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies.

RESULTS:

Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively.

CONCLUSIONS:

Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research.

PMID:
30726294
DOI:
10.1371/journal.pone.0211690
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Conflict of interest statement

The authors have declared that no competing interests exist.

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