Journal Article

Large-scale association analysis identifies new risk loci for coronary artery disease

Lundmark, Per, Pastinen, Tomi, Nikus, Kjell, Lee, Jong-Young, Morris, Andrew D, Rumpf, Moritz P, de Faire, Ulf, Kooner, Jaspal S, Tan, Sian-Tsung, Mihailov, Evelin, Thompson, John R, Maouche, Seraya, McCarthy, Mark I, Peden, John F, Arveiler, Dominique, Basart, Hanneke, Hunt, Sarah E, Farrall, Martin, Erdmann, Jeanette, Schadt, Eric, Hengstenberg, Christian, Lokki, Marja-Liisa, Stefansson, Kari, Samani, Nilesh J, Cazier, Jean-Baptiste, Ho, Weang K, Rafelt, Suzanne, Hazen, Stanley L, Peters, Annette, Rader, Daniel J, Kristiansson, Kati, Tikkanen, Emmi, Pedersen, Nancy L, Esko, Tõnu, König, Inke R, Kuulasmaa, Kari, Shungin, Dmitry, Gauguier, Dominique, Absher, Devin, Schäfer, Arne, Kolovou, Genovefa, Balmforth, Anthony J, Van Zuydam, Natalie, Thorgeirsson, Gudmundur, Sandhu, Manjinder S, Quertermous, Thomas, Kähönen, Mika, Strawbridge, Rona J, Barroso, Inês, Leander, Karin, Brambilla, Paolo, Laaksonen, Reijo, Boehm, Bernhard O, Langenberg, Claudia, Rosinger, Silke, Shah, Svati H, Boerwinkle, Eric, Rasheed, Asif, Dehghan, Abbas, Voight, Benjamin F, Ferrières, Jean, Lind, Lars, Chambers, John C, Gustafsson, Stefa

2013

Overview

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways. Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants ( r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/205 / 631/208/2489/144 / 692/699/75/593/15 / Adult / Aged / Agriculture / Animal Genetics and Genomics / Asian People / Biomedicine / Blood pressure / Cancer Research / Cardiology and Cardiovascular Disease / Cardiovascular disease / Cell Line / Cholesterol / Clinical Medicine / Coronary Artery Disease - genetics / Coronary heart disease / Disease susceptibility / Endocrinology and Diabetes / Endokrinologi och diabetes / Female / Gene expression / Gene Function / Gene Regulatory Networks / Genetic Predisposition to Disease / Genome-Wide Association Study / Genomes / Human Genetics / Humans / Kardiologi och kardiovaskulära sjukdomar / Klinisk medicin / Male / Medical and Health Sciences / Medicin och hälsovetenskap / Meta-analysis / Metabolic disorders / Middle Aged / Pathogenesis / Polymorphism, Single Nucleotide / Quantitative Trait Loci / Risk Factors / Studies / Type 2 diabetes / White People - genetics