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New susceptibility locus for coronary artery disease on chromosome 3q22.3

2009; Nature Portfolio; Volume: 41; Issue: 3 Linguagem: Inglês

10.1038/ng.307

1546-1718

Jeanette Erdmann, Anika Großhennig, Peter S. Braund, Inke R. König, Christian Hengstenberg, Alistair S. Hall, Patrick Linsel‐Nitschke, Sekar Kathiresan, Ben Wright, David‐Alexandre Trégouët, François Cambien, Petra Bruse, Zouhair Aherrahrou, Arnika Kathleen Wagner, Klaus Stark, Stephen M. Schwartz, Veikko Salomaa, Roberto Elosúa, Olle Melander, Benjamin F. Voight, Christopher J. O’Donnell, Leena Peltonen, David S. Siscovick, David Altshuler, Piera Angelica Merlini, Flora Peyvandi, Luisa Bernardinelli, Diego Ardissino, Arne Schillert, Stefan Blankenberg, Tanja Zeller, Philipp S. Wild, Dániel Schwarz, Laurence Tiret, Claire Perret, Stefan Schreiber, Nour Eddine El Mokhtari, Arne Schäfer, Winfried März, Wilfried Renner, Peter Bugert, Harald Klüter, Jürgen Schrezenmeir, Deborah C. Rubin, Stephen G. Ball, Anthony J. Balmforth, H‐Erich Wichmann, Thomas Meitinger, Marcus Fischer, Christa Meisinger, Jens Baumert, Annette Peters, Willem H. Ouwehand, Panos Deloukas, John R. Thompson, Andreas Ziegler, Nilesh J. Samani, Heribert Schunkert,

Glycosylation and Glycoproteins Research

Jeanette Erdmann and colleagues identify a locus on chromosome 3q22.3 associated with coronary artery disease. The SNP with the strongest association is in MRAS, which encodes a membrane-anchored GTP-binding protein. We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in ∼25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 × 10−13; OR = 1.15, 95% CI = 1.11–1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 × 10−7; OR = 1.08, 95% CI = 1.05–1.11).