ng.307

ng.307 - New susceptibility locus for coronary artery...

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Unformatted text preview: New susceptibility locus for coronary artery disease on chromosome 3q22.3 Jeanette Erdmann 1 , Anika Gro hennig 1,2 , Peter S Braund 3 , Inke R Ko nig 2 , Christian Hengstenberg 4 , Alistair S Hall 5 , Patrick Linsel-Nitschke 1 , Sekar Kathiresan 6 , Ben Wright 7 , David-Alexandre Tre goue t 8 , Francois Cambien 8 , Petra Bruse 1 , Zouhair Aherrahrou 1 , Arnika K Wagner 1 , Klaus Stark 4 , Stephen M Schwartz 9 , Veikko Salomaa 10 , Roberto Elosua 11 , Olle Melander 12 , Benjamin F Voight 13 , Christopher J ODonnell 14 , Leena Peltonen 15 , David S Siscovick 9 , David Altshuler 16 , Piera Angelica Merlini 17 , Flora Peyvandi 18 , Luisa Bernardinelli 19,20 , Diego Ardissino 21 , Arne Schillert 2 , Stefan Blankenberg 22 , Tanja Zeller 22 , Philipp Wild 22 , Daniel F Schwarz 2 , Laurence Tiret 8 , Claire Perret 8 , Stefan Schreiber 23 , Nour Eddine El Mokhtari 23 , Arne Scha fer 23 , Winfried Ma rz 2426 , Wilfried Renner 25 , Peter Bugert 27 , Harald Klu ter 27 , Ju rgen Schrezenmeir 28 , Diana Rubin 28 , Stephen G Ball 5 , Anthony J Balmforth 5 , H-Erich Wichmann 29,30 , Thomas Meitinger 31,32 , Marcus Fischer 4 , Christa Meisinger 29 , Jens Baumert 29 , Annette Peters 29 , Willem H Ouwehand 33 , Italian Atherosclerosis, Thrombosis, and Vascular Biology Working Group 34 , Myocardial Infarction Genetics Consortium 34 , Wellcome Trust Case Control Consortium 34 , Cardiogenics Consortium 34 , Panos Deloukas 15 , John R Thompson 7 , Andreas Ziegler 2 , Nilesh J Samani 3 & Heribert Schunkert 1 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 B 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 1.111.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 ( P 4.81 10 7 ; OR 1.08, 95% CI 1.051.11). Recent genome-wide association studies (GWAS) of coronary artery disease (CAD) have focused on a few chromosomal regions with strong signals 14 . We hypothesized that the application of stringent statistical thresholds may have dismissed SNPs with modest effects or low allele frequencies ( Supplementary Fig. 1 and Supplementary Table 1 online). For this study, we started by identifying SNPs meeting a less-stringent cutoff for association ( P r 1 10 3 ) in a new GWAS for myocardial infarction. In stage 1, we genotyped 869,224 autosomal SNPs from the Affymetrix Genome-Wide Human SNP Array 6.0 in 1,222 myocardial infarction cases (German MI Family Study II (GerMIFS II); Supple- mentary Methods online) with premature disease onset and positive family history and 1,298 population-based Germans of European descent. After quality control ( Supplementary Fig. 2 online), 567,119 SNPs remained. The inflation factor estimated for all SNPs that passed quality control is 1.04 (s.e.m.that passed quality control is 1....
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ng.307 - New susceptibility locus for coronary artery...

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