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Atherosclerosis. 2016 Jun;249:83-7. doi: 10.1016/j.atherosclerosis.2016.03.042. Epub 2016 Apr 4.

Update of the effect estimates for common variants associated with carotid intima media thickness within four independent samples: The Bonn IMT Family Study, the Heinz Nixdorf Recall Study, the SAPHIR Study and the Bruneck Study.

Author information

1
Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany.
2
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
3
Institute of Medical Biometry and Statistics (IMBS), University of Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
4
Medizinische Klinik II, St. Vincenz-Krankenhaus, Datteln, Germany; West German Heart and Vascular Center, Department of Cardiology, University Hospital of Essen, Essen, Germany.
5
Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany.
6
IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
7
Department of Epileptology, University of Bonn, Bonn, Germany.
8
IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; Medical Faculty, Deanery of Medicine, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
9
Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
10
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
11
West German Heart and Vascular Center, Department of Cardiology, University Hospital of Essen, Essen, Germany.
12
Cologne Center of Genomics, University of Cologne, Cologne, Germany.
13
Institute of Medical Biometry and Statistics (IMBS), University of Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
14
Department of Neurology, University Hospital Bonn, Bonn, Germany; German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
15
Institute of Medical Biometry and Statistics (IMBS), University of Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Center for Clinical Trials, University of Lübeck, Lübeck, Germany; School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa.
16
Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
17
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: Florian.Kronenberg@i-med.ac.at.

Abstract

Carotid intima media thickness (cIMT) is a marker for subclinical atherosclerosis. The most recent genome-wide association meta-analysis (GWAMA) from the CHARGE consortium identified four genomic regions showing either significant (ZHX2, APOC1, PINX1) or suggestive evidence (SLC17A4) for an association. Here we assess these four cIMT loci in a pooled analysis of four independent studies including 5446 individuals by providing updated unbiased effect estimates of the cIMT association signals. The pooled estimates of our four independent samples pointed in the same direction and were similar to those of the GWAMA. When updating the independent second stage replication results from the earlier CHARGE GWAMA by our estimates, effect size estimates were closer to those of the original CHARGE discovery. A fine-mapping approach within a ±50 kb region around each lead SNP from CHARGE revealed 27 variants with larger estimated effect sizes than the lead SNPs but only three of them showed a r(2) > 0.40 with these respective lead SNPs from CHARGE. Some variants are located within potential functional loci.

KEYWORDS:

Carotid intima-media thickness; Fine-mapping; Genetic association

[Indexed for MEDLINE]

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