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

  • Marie H Geisel
  • Stefan Coassin
  • Nicole Heßler
  • Marcus Bauer
  • Lewin Eisele
  • Raimund Erbel
  • Margot Haun
  • Frauke Hennig
  • Susanna Moskau-Hartmann
  • Barbara Hoffmann
  • Karl-Heinz Jöckel
  • Lyudmyla Kedenko
  • Stefan Kiechl
  • Barbara Kollerits
  • Amir-Abbas Mahabadi
  • Susanne Moebus
  • Gudrun Nürnberg
  • Peter Nürnberg
  • Bernhard Paulweber
  • Maren Andrea Vens
  • Johann Willeit
  • Karin Willeit
  • Thomas Klockgether
  • Andreas Ziegler
  • André Scherag
  • Florian Kronenberg

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.

Bibliografische Daten

OriginalspracheEnglisch
ISSN0021-9150
DOIs
StatusVeröffentlicht - 06.2016
PubMed 27085157