Atherosclerosis 219 (2011) 684–689
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Atherosclerosis
journal homepage: www.elsevier.com/locate/atherosclerosis
Novel associations for coronary artery disease derived from genome wide
association studies are not associated with increased carotid intima-media
thickness, suggesting they do not act via early atherosclerosis or vessel
remodeling
Lucia Conde
a,1
, Steve Bevan
b,1
, Matthias Sitzer
c
, Norman Klopp
d
, Thomas Illig
d
, Joachim Thiery
e
,
Joachim Seissler
f
, Jens Baumert
g
, Olli Raitakari
h
, Mika Kähönen
i
, Leo-Pekka Lyytikäinen
j
,
Reijo Laaksonen
j
, Jorma Viikari
k
, Terho Lehtimäki
j
, Wolfgang Koernig
l
, Eran Halperin
m,n
,
Hugh S. Markus
b,∗
a
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA
b
Stroke and Dementia Research Centre, St. George’s University of London, London, UK
c
Department of Neurology, JW Goeth University, Frankfurt, Germany
d
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
e
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany
f
Institute of Diabetologia, Department of Internal Medicine, Ludwig-Maximilians-Universität München, Munich, Germany
g
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
h
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and the Department of Clinical Physiology, Turku University Hospital, Turku, Finland
i
Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland
j
Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland
k
Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland
l
Department of Internal Medicine II-Cardiology, Medical Centre, University of Ulm, Ulm, Germany
m
Edmond J. Safra Bioinformatics Program, Tel-Aviv University, Israel
n
The International Computer Science Institute, Berkeley, CA, USA
article info
Article history:
Received 27 May 2011
Received in revised form 15 August 2011
Accepted 16 August 2011
Available online 25 August 2011
Keywords:
Coronary artery disease
Atherosclerosis
Genetics
Myocardial infarction
Intima-media thickness
Genome wide association
abstract
Background: Recent genome-wide association studies (GWAS) have identified associations with myocar-
dial infarction and coronary artery disease (CAD), but the mechanisms underlying these associations
remain largely unclear. Carotid intima-media thickness (IMT) is a measure of early arterial remodeling
and arteriosclerosis. Therefore, if CAD associated SNPs are also associated with carotid IMT; it suggests
that they are acting via the early stages of the atherosclerotic process.
Methods: In three large community based independent populations (CAPS, KORA and Young Finns) of
European ancestry in which common carotid IMT had been measured (total 4961 individuals), we deter-
mined whether SNPs that have been associated with CAD in GWAS studies are also associated with carotid
IMT. Associations with plaque were not examined.
Results: We identified 11 SNPs and one haplotype previously associated with CAD. None of these were
associated with common carotid IMT.
Conclusions: We found no evidence that SNPs associated with CAD on GWAS are also associated with
carotid IMT. This suggests these genetic associations are not acting via early vessel remodeling or early
arteriosclerosis.
© 2011 Elsevier Ireland Ltd. All rights reserved.
∗
Corresponding author at: St. George’s University of London, Cranmer Terrace,
London SW17 ORE, UK. Tel.: +44 2087252735; fax: +44 2087252950.
E-mail address: hmarkus@sgul.ac.uk (H.S. Markus).
1
These authors contributed equally.
1. Introduction
Recent genome-wide association studies (GWAS) have identi-
fied a number of single nucleotide polymorphisms (SNPs), which
are associated with myocardial infarction and coronary artery dis-
ease (CAD) [1–6]. These associations have been replicated across
multiple populations. However, for most of these SNPs the mech-
anisms underlying the associations remains unclear. Genetic risk
0021-9150/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2011.08.031