Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Andrew D. Johnson | P. Elliott | C. Sudlow | J. Danesh | M. Fornage | M. Nalls | C. Carty | A. Reiner | U. Thorsteinsdóttir | K. Stefánsson | V. Salomaa | S. Yusuf | M. Kanai | Y. Kamatani | Y. Okada | P. Ridker | D. Chasman | V. Gudnason | E. Schadt | P. Ellinor | R. Sacco | P. D. de Bakker | C. Schmidt | C. Kooperberg | K. Rexrode | D. Leys | E. Tai | J. Björkegren | Qiong Yang | G. Thorleifsson | P. Rothwell | E. Ingelsson | D. Trégouët | P. Almgren | O. Melander | J. Rotter | F. Hsu | M. O’Donnell | A. Havulinna | Wei-Min Chen | T. Harris | M. Dichgans | P. Amouyel | S. Kittner | B. Kissela | Carlos Cruchaga | S. Pulit | C. Langefeld | N. Wareham | K. Rice | S. Gustafsson | T. Pastinen | Robert D. Brown | J. Jukema | C. Tzourio | M. Ikram | D. Saleheen | James G. Wilson | J. Bis | X. Jian | J. Kooner | S. Rich | J. Howson | E. Holliday | L. Launer | Julie A. Johnson | S. Heckbert | G. Howard | T. Mosley | S. Seshadri | F. Takeuchi | Q. Duan | C. Langenberg | J. Chambers | N. Kato | P. van der Harst | U. Schminke | A. Lindgren | P. McArdle | B. Mitchell | H. Markus | D. Sanghera | T. Ninomiya | J. Maguire | A. Butterworth | G. Paré | J. Hata | T. Rundek | G. Chauhan | W. Longstreth | D. Woo | S. Debette | M. Walters | S. Lubitz | S. Trompet | S. W. van der Laan | J. Haessler | L. Lange | V. Thijs | T. Tatlisumak | S. Engelter | Cohorts for Heart | J. Hopewell | M. Civelek | A. Manichaikul | A. Mishra | A. Rolfs | O. Benavente | N. Rost | H. Ay | J. Rosand | A. Giese | J. Lee | A. Słowik | D. Strbian | G. Falcone | I. Férnandez-Cadenas | C. Carrera | C. Jern | S. Wassertheil-Smoller | Jiang He | M. Irvin | S. Sakaue | M. Sale | R. Malik | M. Sargurupremraj | N. Smith | C. Roselli | M. den Hoed | K. Wiggins | L. Rutten-Jacobs | J. Meschia | R. Gottesman | Pankaj Sharma | D. Kleindorfer | R. Grewal | Keith L. Keene | B. Worrall | M. Traylor | S. Bevan | G. Boncoraglio | M. Chong | R. Lemmens | T. Ago | Veronica Codoni | J. Cole | P. Magnusson | A. Ruusalepp | C. Anderson | I. Cotlarciuc | Ahamad Hassan | Wei-Yu Lin | E. Lorentzen | B. Sapkota | C. Tanislav | Simon Koplev | I. Christophersen | Uk Young Lacunar Dna Study | Traci M Bartz | J. Jiménez-Conde | S. Gretarsdottir | M. Kubo | C. V. van Duijn | B. Psaty | A. Destefano | Kristiina Rannikmäe | C. Lewis | K. Taylor | H. Adams | R. Schmidt | A. Correa | Hyacinth I. Hyacinth | S. Tiedt

[1]  M. Kanai,et al.  Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases , 2018, Nature Genetics.

[2]  Jacqueline K. White,et al.  Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis , 2017, Nature Genetics.

[3]  Henry J. Lin,et al.  Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation , 2017, Nature Genetics.

[4]  C. Sudlow,et al.  Genetic variation at 16q24.2 is associated with small vessel stroke , 2017, Annals of neurology.

[5]  Y. Kamatani,et al.  Genetic Predisposition to Ischemic Stroke , 2017, Stroke.

[6]  A. Mishra,et al.  A Novel Approach for Pathway Analysis of GWAS Data Highlights Role of BMP Signaling and Muscle Cell Differentiation in Colorectal Cancer Susceptibility , 2017, Twin Research and Human Genetics.

[7]  A. Hofman,et al.  Disease variants alter transcription factor levels and methylation of their binding sites , 2016, Nature Genetics.

[8]  Christian Gieger,et al.  Connecting genetic risk to disease end points through the human blood plasma proteome , 2016, Nature Communications.

[9]  Ashutosh Kumar Singh,et al.  Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015 , 2016, The Lancet.

[10]  Ashutosh Kumar Singh,et al.  Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 , 2016, Lancet.

[11]  L. Wilkins.  Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration , 2016, Neurology.

[12]  He Zhang,et al.  Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension , 2016, Nature Genetics.

[13]  A. Tall,et al.  LNK/SH2B3 Loss of Function Promotes Atherosclerosis and Thrombosis. , 2016, Circulation research.

[14]  Tom Michoel,et al.  Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases , 2016, Science.

[15]  Manolis Kellis,et al.  Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases , 2016, Nucleic acids research.

[16]  S. Prabhu,et al.  The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. , 2016, Circulation research.

[17]  K. Okamura,et al.  Human genetic variation database, a reference database of genetic variations in the Japanese population , 2016, Journal of Human Genetics.

[18]  J. Lee,et al.  Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study , 2016, The Lancet Neurology.

[19]  Kaitlin M. Fitzpatrick,et al.  Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke , 2016, Neurology.

[20]  B. Pasaniuc,et al.  Contrasting the genetic architecture of 30 complex traits from summary association data , 2016, bioRxiv.

[21]  S. Brunak,et al.  Familial Atrial Septal Defect and Sudden Cardiac Death: Identification of a Novel NKX2‐5 Mutation and a Review of the Literature , 2015, Congenital heart disease.

[22]  Manolis Kellis,et al.  HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease , 2015, Nucleic Acids Res..

[23]  Feng Xu,et al.  Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information , 2015, Nucleic Acids Res..

[24]  Andrew D. Johnson,et al.  Prediction of Causal Candidate Genes in Coronary Artery Disease Loci , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[25]  Gabor T. Marth,et al.  A global reference for human genetic variation , 2015, Nature.

[26]  Jing He,et al.  Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation , 2015, Nature Genetics.

[27]  Hui Yang,et al.  Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR , 2015, Nature Protocols.

[28]  Sebastian M. Armasu,et al.  A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease , 2015, Nature Genetics.

[29]  M. Dichgans,et al.  Heterozygous HTRA1 mutations are associated with autosomal dominant cerebral small vessel disease. , 2015, Brain : a journal of neurology.

[30]  Joseph K. Pickrell,et al.  Detection and interpretation of shared genetic influences on 42 human traits , 2015, Nature Genetics.

[31]  Sara M. Willems,et al.  The impact of low-frequency and rare variants on lipid levels , 2015, Nature Genetics.

[32]  Jun S. Liu,et al.  The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans , 2015, Science.

[33]  M. Daly,et al.  An Atlas of Genetic Correlations across Human Diseases and Traits , 2015, Nature Genetics.

[34]  K. Hao,et al.  Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism. , 2015, American journal of human genetics.

[35]  Lorna M. Lopez,et al.  Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI , 2015, Circulation. Cardiovascular genetics.

[36]  G. Davey Smith,et al.  Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression , 2015, International journal of epidemiology.

[37]  田原 康玄,et al.  生活習慣病とgenome-wide association study , 2015 .

[38]  Michael Q. Zhang,et al.  Integrative analysis of 111 reference human epigenomes , 2015, Nature.

[39]  J. Hirschhorn,et al.  Biological interpretation of genome-wide association studies using predicted gene functions , 2015, Nature Communications.

[40]  Bernadette A. Thomas,et al.  Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2015, The Lancet.

[41]  S. MacGregor,et al.  VEGAS2: Software for More Flexible Gene-Based Testing , 2014, Twin Research and Human Genetics.

[42]  Wenjie Chen,et al.  GRASP v2.0: an update on the Genome-Wide Repository of Associations between SNPs and phenotypes , 2014, Nucleic Acids Res..

[43]  Gabi Kastenmüller,et al.  SNiPA: an interactive, genetic variant-centered annotation browser , 2014, Bioinform..

[44]  K. Lunetta,et al.  Integrating Genetic, Transcriptional, and Functional Analyses to Identify 5 Novel Genes for Atrial Fibrillation , 2014, Circulation.

[45]  C. Sudlow,et al.  Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12 , 2014, Neurology.

[46]  R. D. de Boer,et al.  Genetic Determinants of P Wave Duration and PR Segment , 2014, Circulation. Cardiovascular genetics.

[47]  Niku Oksala,et al.  A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach , 2014, PLoS genetics.

[48]  Richard Leslie,et al.  GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database , 2014, Bioinform..

[49]  Zoltán Kutalik,et al.  Quality control and conduct of genome-wide association meta-analyses , 2014, Nature Protocols.

[50]  Lisa J. Martin,et al.  Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage. , 2014, American journal of human genetics.

[51]  M. Daly,et al.  LD Score regression distinguishes confounding from polygenicity in genome-wide association studies , 2014, Nature Genetics.

[52]  P. Visscher,et al.  Genetics of rheumatoid arthritis contributes to biology and drug discovery , 2013, Nature.

[53]  Carol Moreno,et al.  Identifying multiple causative genes at a single GWAS locus , 2013, Genome research.

[54]  Aldons J. Lusis,et al.  Identification of CAD candidate genes in GWAS loci and their expression in vascular cells[S] , 2013, Journal of Lipid Research.

[55]  C. Sudlow,et al.  Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study , 2013, Annals of neurology.

[56]  B. Stranger,et al.  Chromatin marks identify critical cell types for fine mapping complex trait variants , 2012, Nature Genetics.

[57]  Jake K. Byrnes,et al.  Bayesian refinement of association signals for 14 loci in 3 common diseases , 2012, Nature Genetics.

[58]  Tanya M. Teslovich,et al.  Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes , 2012, Nature Genetics.

[59]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[60]  K. Lunetta,et al.  Meta-analysis identifies six new susceptibility loci for atrial fibrillation , 2012, Nature Genetics.

[61]  L. Cardon,et al.  Use of genome-wide association studies for drug repositioning , 2012, Nature Biotechnology.

[62]  P. Visscher,et al.  Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits , 2012, Nature Genetics.

[63]  Thomas Lengauer,et al.  BLUEPRINT to decode the epigenetic signature written in blood , 2012, Nature Biotechnology.

[64]  S. Greenberg,et al.  COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. , 2012, American journal of human genetics.

[65]  M. Pirinen,et al.  Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke , 2012, Nature Genetics.

[66]  A. Morris,et al.  Transethnic Meta-Analysis of Genomewide Association Studies , 2011, Genetic epidemiology.

[67]  W. Rathmann,et al.  Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque , 2011, Nature Genetics.

[68]  Christian Gieger,et al.  Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure , 2011, Nature Genetics.

[69]  Tom R. Gaunt,et al.  Genetic Variants in Novel Pathways Influence Blood Pressure and Cardiovascular Disease Risk , 2011, Nature.

[70]  P. Sham,et al.  Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases , 2011, Genetic epidemiology.

[71]  Tien Yin Wong,et al.  Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians , 2011, Nature Genetics.

[72]  Eric Boerwinkle,et al.  Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25 , 2010, Circulation.

[73]  P. Visscher,et al.  A versatile gene-based test for genome-wide association studies. , 2010, American journal of human genetics.

[74]  Yun Li,et al.  METAL: fast and efficient meta-analysis of genomewide association scans , 2010, Bioinform..

[75]  Christian Gieger,et al.  Genome-wide association study of PR interval , 2010, Nature Genetics.

[76]  Renata C. Geer,et al.  The NCBI BioSystems database , 2009, Nucleic Acids Res..

[77]  C. Gieger,et al.  A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke , 2009, Nature Genetics.

[78]  Andrew D. Johnson,et al.  SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap , 2008, Bioinform..

[79]  Olha Koval,et al.  Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease , 2008, Proceedings of the National Academy of Sciences.

[80]  Jon Wakefield,et al.  A Bayesian measure of the probability of false discovery in genetic epidemiology studies. , 2007, American journal of human genetics.

[81]  Eric E. Smith,et al.  Variants conferring risk of atrial fibrillation on chromosome 4q25 , 2007, Nature.

[82]  J. Sundberg,et al.  Role of COL4A1 in small-vessel disease and hemorrhagic stroke. , 2006, The New England journal of medicine.

[83]  D. Wishart,et al.  DrugBank: a comprehensive resource for in silico drug discovery and exploration , 2005, Nucleic Acids Res..

[84]  A. Gramolini,et al.  Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death , 2003, Nature.

[85]  V. Feigin,et al.  Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century , 2003, The Lancet Neurology.

[86]  P. Bork,et al.  Human non-synonymous SNPs: server and survey. , 2002, Nucleic acids research.

[87]  J. Seidman,et al.  Congenital heart disease caused by mutations in the transcription factor NKX2-5. , 1998, Science.

[88]  Aric Invest.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators , 1989 .

[89]  Y. Kamatani,et al.  Genetic Predisposition to Ischemic Stroke A Polygenic Risk Score , 2017 .

[90]  Antigha Okon Bassey,et al.  Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders , 2014 .

[91]  Jun S. Liu,et al.  Genetics of rheumatoid arthritis contributes to biology and drug discovery , 2013 .

[92]  Ewan Birney,et al.  Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells. , 2012, Genome research.

[93]  S. Henikoff,et al.  Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm , 2009, Nature Protocols.

[94]  S. Tsuji,et al.  Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. , 2009, The New England journal of medicine.

[95]  Mulin Jun Li,et al.  Nature Genetics Advance Online Publication a N a Ly S I S the Support of Human Genetic Evidence for Approved Drug Indications , 2022 .