TY - JOUR
T1 - Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations
AU - Andersson, Charlotte
AU - Lukács Krogager, Maria
AU - Kuhr Skals, Regitze
AU - Rosenbaum Appel, Emil Vincent
AU - Theil Have, Christian
AU - Grarup, Niels
AU - Pedersen, Oluf
AU - Jeppesen, Jørgen L
AU - Pedersen, Ole Dyg
AU - Dominguez, Helena
AU - Dixen, Ulrik
AU - Engstrøm, Thomas
AU - Tønder, Niels
AU - Roden, Dan M
AU - Stender, Steen
AU - Gislason, Gunnar H
AU - Enghusen-Poulsen, Henrik
AU - Hansen, Torben
AU - Køber, Lars
AU - Torp-Pedersen, Christian
AU - Weeke, Peter E
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061158930&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0211690
DO - 10.1371/journal.pone.0211690
M3 - Journal article
C2 - 30726294
SN - 1932-6203
VL - 14
JO - PLOS ONE
JF - PLOS ONE
IS - 2
M1 - e0211690
ER -