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

TY - JOUR

T1 - 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

AU - Geisel, Marie H

AU - Coassin, Stefan

AU - Heßler, Nicole

AU - Bauer, Marcus

AU - Eisele, Lewin

AU - Erbel, Raimund

AU - Haun, Margot

AU - Hennig, Frauke

AU - Moskau-Hartmann, Susanna

AU - Hoffmann, Barbara

AU - Jöckel, Karl-Heinz

AU - Kedenko, Lyudmyla

AU - Kiechl, Stefan

AU - Kollerits, Barbara

AU - Mahabadi, Amir-Abbas

AU - Moebus, Susanne

AU - Nürnberg, Gudrun

AU - Nürnberg, Peter

AU - Paulweber, Bernhard

AU - Vens, Maren Andrea

AU - Willeit, Johann

AU - Willeit, Karin

AU - Klockgether, Thomas

AU - Ziegler, Andreas

AU - Scherag, André

AU - Kronenberg, Florian

N1 - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PY - 2016/6

Y1 - 2016/6

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.atherosclerosis.2016.03.042

DO - 10.1016/j.atherosclerosis.2016.03.042

M3 - SCORING: Journal article

C2 - 27085157

VL - 249

SP - 83

EP - 87

JO - ATHEROSCLEROSIS

JF - ATHEROSCLEROSIS

SN - 0021-9150

ER -