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Rigshospitalet - a part of Copenhagen University Hospital
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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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  • Charlotte Andersson
  • Maria Lukács Krogager
  • Regitze Kuhr Skals
  • Emil Vincent Rosenbaum Appel
  • Christian Theil Have
  • Niels Grarup
  • Oluf Pedersen
  • Jørgen L Jeppesen
  • Ole Dyg Pedersen
  • Helena Dominguez
  • Ulrik Dixen
  • Thomas Engstrøm
  • Niels Tønder
  • Dan M Roden
  • Steen Stender
  • Gunnar H Gislason
  • Henrik Enghusen-Poulsen
  • Torben Hansen
  • Lars Køber
  • Christian Torp-Pedersen
  • Peter E Weeke
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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.

Original languageEnglish
Article numbere0211690
JournalPLoS One
Volume14
Issue number2
ISSN1932-6203
DOIs
Publication statusPublished - 1 Feb 2019

ID: 56478809