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

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@article{f28a78865b7e4ea7a6c5bc3b7580188b,
title = "Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations",
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.",
author = "Charlotte Andersson and {Luk{\'a}cs Krogager}, Maria and {Kuhr Skals}, Regitze and {Rosenbaum Appel}, {Emil Vincent} and {Theil Have}, Christian and Niels Grarup and Oluf Pedersen and Jeppesen, {J{\o}rgen L} and Pedersen, {Ole Dyg} and Helena Dominguez and Ulrik Dixen and Thomas Engstr{\o}m and Niels T{\o}nder and Roden, {Dan M} and Steen Stender and Gislason, {Gunnar H} and Henrik Enghusen-Poulsen and Torben Hansen and Lars K{\o}ber and Christian Torp-Pedersen and Weeke, {Peter E}",
year = "2019",
month = "2",
day = "1",
doi = "10.1371/journal.pone.0211690",
language = "English",
volume = "14",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

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

VL - 14

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 2

M1 - e0211690

ER -

ID: 56478809