Volume 11, Issue 11, Pages (November 2012)

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Volume 11, Issue 11, Pages 951-962 (November 2012) Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies  Matthew Traylor, MSc, Martin Farrall, FRCPath, Elizabeth G Holliday, PhD, Cathie Sudlow, FRCP, Jemma C Hopewell, PhD, Yu-Ching Cheng, PhD, Myriam Fornage, PhD, M Arfan Ikram, MD, Rainer Malik, PhD, Steve Bevan, PhD, Unnur Thorsteinsdottir, PhD, Mike A Nalls, PhD, WT Longstreth, MD, Kerri L Wiggins, MS, Sunaina Yadav, MSc, Eugenio A Parati, MD, Anita L DeStefano, PhD, Bradford B Worrall, MD, Steven J Kittner, MD, Muhammad Saleem Khan, MSc, Alex P Reiner, MD, Anna Helgadottir, MD, Sefanja Achterberg, PhD, Israel Fernandez-Cadenas, PhD, Sherine Abboud, MD, Reinhold Schmidt, MD, Matthew Walters, MD, Wei-Min Chen, PhD, E Bernd Ringelstein, MD, Martin O'Donnell, MD, Weang Kee Ho, PhD, Joanna Pera, MD, Robin Lemmens, MD, Bo Norrving, MD, Peter Higgins, MRCP, Marianne Benn, MD, Michele Sale, PhD, Gregor Kuhlenbäumer, MD, Alexander S F Doney, PhD, Astrid M Vicente, PhD, Hossein Delavaran, MD, Ale Algra, MD, Gail Davies, PhD, Sofia A Oliveira, PhD, Colin N A Palmer, PhD, Ian Deary, PhD, Helena Schmidt, MD, Massimo Pandolfo, MD, Joan Montaner, MD, Cara Carty, PhD, Paul I W de Bakker, PhD, Konstantinos Kostulas, MD, Jose M Ferro, MD, Natalie R van Zuydam, MSc, Einar Valdimarsson, MD, Børge G Nordestgaard, MD, Arne Lindgren, MD, Vincent Thijs, MD, Agnieszka Slowik, MD, Danish Saleheen, MD, Guillaume Paré, MD, Klaus Berger, MD, Gudmar Thorleifsson, PhD, Albert Hofman, MD, Thomas H Mosley, PhD, Braxton D Mitchell, PhD, Karen Furie, MD, Robert Clarke, FRCP, Christopher Levi, MD, Sudha Seshadri, MD, Andreas Gschwendtner, MD, Giorgio B Boncoraglio, MD, Pankaj Sharma, PhD, Joshua C Bis, PhD, Solveig Gretarsdottir, PhD, Bruce M Psaty, Peter M Rothwell, FMedSci, Jonathan Rosand, MD, James F Meschia, MD, Kari Stefansson, MD, Martin Dichgans, MD, Dr Hugh S Markus, DM  The Lancet Neurology  Volume 11, Issue 11, Pages 951-962 (November 2012) DOI: 10.1016/S1474-4422(12)70234-X Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 1 Flow diagram of METASTROKE analyses GWAS=genome-wide association study. SNP=single nucleotide polymorphism. The Lancet Neurology 2012 11, 951-962DOI: (10.1016/S1474-4422(12)70234-X) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 2 Manhattan plots of –log10(p) against genomic position for principal analyses (A) All ischaemic stroke. (B) Large-vessel disease. (C) Cardioembolic stroke. (D) Small-vessel disease. Genome-wide meta-analysis association results by genomic position for the four main analyses. The Lancet Neurology 2012 11, 951-962DOI: (10.1016/S1474-4422(12)70234-X) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 3 Plots of conditional analysis regions before and after conditioning on lead SNP SNP=single nucleotide polymorphism. Plots of association signals around loci investigated in conditional analyses in subtypes in which they were discovered for the meta-analysed discovery samples. SNPs are coloured on the basis of their correlation (r2) with the labelled top SNP, which has the smallest p value in the region. The fine-scale recombination rates estimated from HapMap data are marked in red, with genes marked below by horizontal blue lines. Arrows on the horizontal blue lines show the direction of transcription, and rectangles are exons. (A,C,E) Regions from discovery meta-analyses. (B,D,F) Same regions as A,C,E after conditioning on the lead SNP from the region. The Lancet Neurology 2012 11, 951-962DOI: (10.1016/S1474-4422(12)70234-X) Copyright © 2012 Elsevier Ltd Terms and Conditions