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 r2 > 0.40 with these respective lead SNPs from CHARGE. Some variants are located within potential functional loci.
| Original language | English |
|---|---|
| Journal | Atherosclerosis |
| Volume | 249 |
| Pages (from-to) | 83-87 |
| Number of pages | 5 |
| ISSN | 0021-9150 |
| DOIs | |
| Publication status | Published - 01.06.2016 |
Funding
HG and AS were supported by a grant from the German Research Foundation ( SCHE 1648/1-3 ). AS was also supported by a BMBF grant from the Center for Sepsis Control and Care (FKZ: 01EO1002 ; 01EO1502 ). TK and AZ received funding from the German Research Foundation ( KL 782/11-1 , ZI 597/16-1 ) for the Bonn IMT Family Study. The Bruneck Study is part of the excellence initiative (Competence Centers for Excellent Technologies - COMET) of the Austrian Research Promotion Agency FFG: “Research Center of Excellence in Vascular Ageing – Tyrol, VASCage” (K-Project No. 843536) funded by the BMVIT , BMWFW , Wirtschaftsagentur Wien and Standortagentur Tirol . The SAPHIR study was supported by the Kamilo-Eisner Stiftung and Salzburger Forschungsgesellschaft . We thank the Heinz Nixdorf Foundation, Germany (chairman: M. Nixdorf, past chairman: Dr. Jur. G. Schmidt) for their generous support of this study, the German Ministry of Education and Science (BMBF), the German Research Council (DFG) ( SI-236/8-1, SI-236/9-1, ER155/6-2 ). We are indebted to the investigative group and the study personnel of the Heinz Nixdorf Recall study, in particular EM Beck, IMIBE, Dr. M. Bröcker-Preuss from the Department of Clinical Chemistry and Laboratory Medicine. Advisory board: T. Meinerz, Hamburg (Chair); M. Blettner, Mainz; C. Bode, Freiburg; P. J. de Feyter, Rotterdam, Zürich, Niederlande; B. Güntert, Hall i.T., Schweiz; F. Gutzwiller, Schweiz; H. Heinen, Bonn; O. Hess, Bern, Schweiz; B. Klein, Essen; H. Löwel, Neuherberg; M. Reiser, München; G. Schmidt, Essen; M. Schwaiger, München; C. Steinmüller, Bonn; T. Theorell, Stockholm, Schweden; S. N. Willich, Berlin. Criteria and end point committee: C. Bode, Freiburg (Chair), K. Berger, Münster; H. R. Figulla, Jena; C. Hamm, Bad Nauheim; P. Hanrath, Aachen; W. Köpcke, Münster; C. Weimar, Essen; A. Zeiher, Frankfurt. cIMT measurements were done in the framework of the AirCimt study (DFG HO3314/2–3 and SCHE1648/1–3). We received support of the Ministry of Innovation, Science and Research, Nordrhine Westfalia for complete genotyping of the HNR cohort. We also thank the project manager N. Pundt. The manuscript includes part of the doctor thesis of the students S. Baar, A. Müller-Faber, V. May and J.-M. Worm. They performed the semi-automatic detection of the CIMT using the software “Artery Measurement System (AMS) II”. The students put much effort in the training and reading process, which was supervised by F. Hennig who was also responsible for the organization of the readings and she additionally performed the quality checks of the measurements.
