title: 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.
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.
authors.affiliation: 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.
authors.forename: Marie H
authors.initials: MH
authors.lastname: Geisel
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Coassin
authors.affiliation: Institute of Medical Biometry and Statistics (IMBS), University of Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Heßler
authors.affiliation: Medizinische Klinik II, St. Vincenz-Krankenhaus, Datteln, Germany; West German Heart and Vascular Center, Department of Cardiology, University Hospital of Essen, Essen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany.
authors.forename: Lewin
authors.initials: L
authors.lastname: Eisele
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Margot
authors.initials: M
authors.lastname: Haun
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Hennig
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Moskau-Hartmann
authors.affiliation: IUF Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; Medical Faculty, Deanery of Medicine, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Kedenko
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kollerits
authors.affiliation: West German Heart and Vascular Center, Department of Cardiology, University Hospital of Essen, Essen, Germany.
authors.forename: Amir-Abbas
authors.initials: AA
authors.lastname: Mahabadi
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.affiliation: Cologne Center of Genomics, University of Cologne, Cologne, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.affiliation: Cologne Center of Genomics, University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.affiliation: 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.
authors.forename: Maren
authors.initials: M
authors.lastname: Vens
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Willeit
authors.affiliation: Department of Neurology, University Hospital Bonn, Bonn, Germany; German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.affiliation: Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: 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.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D002874:Chromosome Mapping; D003627:Data Interpretation, Statistical; D005192:Family Health; D005260:Female; D055106:Genome-Wide Association Study; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012107:Research Design
keywords: Carotid intima-media thickness; Fine-mapping; Genetic association