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

Citation for published version: Malik, R, Chauhan, G, Traylor, M, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, A-K, van der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, TM, Benavente, OR, Bevan, S, Boncoraglio, GB, Brown Jnr, RD, Butterworth, AS, Carrera, C, International Genomics of Blood Pressure (iGEN-BP) Consortium, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, INVENT Consortium, STARNET, Guðnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, F-C, Hyacinth, HI, Arfan Ikram, M, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, J-M, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, KM, Rich, SS, Ridker, PM, Rost, NS, Rothwell, PM, Rotter, JI, Rundek, T, Sacco, RL, Sakaue, S, Sale, MM, Salomaa, V, Sapkota, BR, Schmidt, R, Oliver Schmidt, C, Schminke, U, Sharma, P, Slowik, A, Sudlow, CLM, Tatlisumak, T, Tanislav, C, Taylor, KD, Thijs, VNS, Thorleifsson, G, Thorsteinsdottir, U, Tiedt, S, Trompet, S, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, WassertheilSmoller, S, Wilson, JG, Wiggins, KL, Yang, Q, Yusuf, S, Bis, JC, Pastinen, T, Ruusalepp, A, Schadt, EE, Koplev, S, Björkegren , JLM, Codoni, V, Civelek, M, Smith, NL, Trégouët, DA, Christophersen, IE, Roselli, C, Lubitz, SA, Ellinor, PT, Shyong Tai, E, Kooner, JS, Kato, N, He, J, van der Harst, P, Elliott, P, Chambers, JC, Takeuchi, F, Johnson, AD, BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPICCVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium (ISGC), METASTROKE Consortium, The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, NINDS Stroke Genetics Network (SiGN), UK Young Lacunar DNA Study, MEGASTROKE Consortium, Sanghera, DK, Melander, O, Jern, C, Strbian, D, Fernandez-Cadenas, I, Longstreth Jr, WT, Rolfs, A, Hata, J, Woo , D, Rosand, J, Pare, G, Hopewell, JC, Saleheen, D, Stefansson, K, Worrall, BB, Kittner, SJ, Seshadri, S, Fornage, M, Markus, HS, Howson, JMM, Kamatani, Y, Debette, S, Dichgans, M, AFGen Consortium & Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium 2018, 'Multi-ancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes', Nature Genetics, vol. 50, no. 4, pp. 524–537. https://doi.org/10.1038/s41588-018-0058-3

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

[1]  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.

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

[3]  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.

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

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

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

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

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

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

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

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

[12]  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.

[13]  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..

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

[15]  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..

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

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

[18]  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.

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

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

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

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

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

[24]  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.

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

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

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

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

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

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

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

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

[33]  R. Mägi,et al.  Quality control and conduct of genome-wide association meta-analyses , 2014, Nature Protocols.

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

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

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

[37]  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.

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

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

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

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

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

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

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

[45]  S. Greenberg,et al.  COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. , 2012, American Journal of Human Genetics.

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

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

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

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

[50]  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.

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

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

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

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

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

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

[57]  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.

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

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

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

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

[62]  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.

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

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

[65]  Melissa C. Greven,et al.  An integrated encyclopedia of DNA elements in the human genome , 2014 .

[66]  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.

[67]  Nature Genetics Advance Online Publication , 2022 .

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