1. Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease
- Author
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Ghosh, Sujoy, Vivar, Juan, Nelson, Christopher P, Willenborg, Christina, Segrè, Ayellet V, Mäkinen, Ville-Petteri, Nikpay, Majid, Erdmann, Jeannette, Blankenberg, Stefan, O'Donnell, Christopher, März, Winfried, Laaksonen, Reijo, Stewart, Alexandre FR, Epstein, Stephen E, Shah, Svati H, Granger, Christopher B, Hazen, Stanley L, Kathiresan, Sekar, Reilly, Muredach P, Yang, Xia, Quertermous, Thomas, Samani, Nilesh J, Schunkert, Heribert, Assimes, Themistocles L, and McPherson, Ruth
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Genetics ,Human Genome ,Atherosclerosis ,Heart Disease ,Aetiology ,2.1 Biological and endogenous factors ,Underpinning research ,1.1 Normal biological development and functioning ,Coronary Artery Disease ,Genome-Wide Association Study ,Humans ,coronary artery disease ,pathway analysis ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
ObjectiveGenome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks.Approaches and resultsUsing pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication P
- Published
- 2015