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Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) StudyClinical Perspective by Michael Preuss, Inke R. König,

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Presentation on theme: "Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) StudyClinical Perspective by Michael Preuss, Inke R. König,"— Presentation transcript:

1 Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) StudyClinical Perspective by Michael Preuss, Inke R. König, John R. Thompson, Jeanette Erdmann, Devin Absher, Themistocles L. Assimes, Stefan Blankenberg, Eric Boerwinkle, Li Chen, L. Adrienne Cupples, Alistair S. Hall, Eran Halperin, Christian Hengstenberg, Hilma Holm, Reijo Laaksonen, Mingyao Li, Winfried März, Ruth McPherson, Kiran Musunuru, Christopher P. Nelson, Mary Susan Burnett, Stephen E. Epstein, Christopher J. O'Donnell, Thomas Quertermous, Daniel J. Rader, Robert Roberts, Arne Schillert, Kari Stefansson, Alexandre F.R. Stewart, Gudmar Thorleifsson, Benjamin F. Voight, George A. Wells, Andreas Ziegler, Sekar Kathiresan, Muredach P. Reilly, Nilesh J. Samani, and Heribert Schunkert Circ Genom Precis Med Volume 3(5): October 19, 2010 Copyright © American Heart Association, Inc. All rights reserved.

2 Workflow of CARDIoGRAM.
Workflow of CARDIoGRAM. Analyses are performed in every study separately by the statistical group and then submitted to the central database. The analysis group checks the data quality within each study and queries individual studies on summary data. Once the initial quality control has been performed and data summaries are consistent across individual studies, these quality-controlled data are updated in the database and used for meta-analysis. Michael Preuss et al. Circ Cardiovasc Genet. 2010;3: Copyright © American Heart Association, Inc. All rights reserved.

3 Estimated power of the meta-analysis.
Estimated power of the meta-analysis. Power for different MAFs and ORs at a P value of 5×10−8 (n= cases and controls). Michael Preuss et al. Circ Cardiovasc Genet. 2010;3: Copyright © American Heart Association, Inc. All rights reserved.

4 Estimated power for the replication.
Estimated power for the replication. Power for different MAFs and ORs. Critical P value for a 1-sided test, 0.05×2=0.1 adjusted for the testing of 30 regions (n= cases and controls). Michael Preuss et al. Circ Cardiovasc Genet. 2010;3: Copyright © American Heart Association, Inc. All rights reserved.

5 Forest plots for SNPs on chromosome 9p21.
Forest plots for SNPs on chromosome 9p21. Random effects (RE) models were calculated for SNPs rs (risk allele=C), rs (risk allele=G), and rs (risk allele=G); the fixed effects (FE) model was calculated for SNP rs (risk allele=C). Heterogeneity between the studies is indicated by I2, and for every study, it is indicated whether the respective SNP was genotyped (G) or imputed (I) or a mixture of genotyped and imputed (NA). Michael Preuss et al. Circ Cardiovasc Genet. 2010;3: Copyright © American Heart Association, Inc. All rights reserved.

6 Results for subgroup association analysis for SNP rs1333049.
Results for subgroup association analysis for SNP rs Shown are ORs with 95% CIs comparing female cases versus female controls, male cases versus male controls, old cases (≥50 years) versus all controls, and young cases (<50 years) versus all controls. Numbers below the x axis denote P values, fixed effects (FE) or random effects (RE) models, and number of cases/controls. Michael Preuss et al. Circ Cardiovasc Genet. 2010;3: Copyright © American Heart Association, Inc. All rights reserved.


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