Genomewide Association Studies of Stroke
Year: 2009
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The genes underlying the risk of stroke in the general population remain undetermined. METHODS: We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [+/-SD] age, 63+/-8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons. RESULTS: Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke (P<5x10(-8)). NINJ2 encodes an adhesion molecule expressed in glia and shows increased expression after nerve injury. Direct genotyping showed that rs12425791 was associated with an increased risk of total (i.e., all types) and ischemic stroke, with hazard ratios of 1.30 (95% confidence interval [CI], 1.19 to 1.42) and 1.33 (95% CI, 1.21 to 1.47), respectively, yielding population attributable risks of 11% and 12% in the discovery cohorts. Corresponding hazard ratios were 1.35 (95% CI, 1.01 to 1.79; P=0.04) and 1.42 (95% CI, 1.06 to 1.91; P=0.02) in the large cohort of black persons and 1.17 (95% CI, 1.01 to 1.37; P=0.03) and 1.19 (95% CI, 1.01 to 1.41; P=0.04) in the Dutch sample; the results of an underpowered analysis of the smaller black cohort were nonsignificant. CONCLUSIONS: A genetic locus on chromosome 12p13 is associated with an increased risk of stroke.
Source: New England Journal of Medicine
Authors: M. Arfan Ikram, Sudha Seshadri, Joshua C. Bis, Myriam Fornage, Anita L. DeStefano, Yurii S. Aulchenko, Stephanie Debette, Thomas Lumley, Aaron R. Folsom, Evita G. van den Herik, Michiel J. Bos, Alexa Beiser, Mary Cushman, Lenore J. Launer, Eyal Shahar, Maksim Struchalin, Yangchun Du, Nicole L. Glazer, Wayne D. Rosamond, Fernando Rivadeneira, Margaret Kelly-Hayes, Oscar L. Lopez, Josef Coresh, Albert Hofman, Charles DeCarli, Susan R. Heckbert, Peter J. Koudstaal, Qiong Yang, Nicholas L. Smith, Carlos S. Kase, Kenneth Rice, Talin Haritunians, Gerwin Roks, Paul L.M. de Kort, Kent D. Taylor, Lonneke M. de Lau, Ben A. Oostra, Andre G. Uitterlinden, Jerome I. Rotter, Eric Boerwinkle, Bruce M. Psaty, Thomas H. Mosley, Cornelia M. van Duijn, Monique M.B. Breteler, W.T. Longstreth, Philip A. Wolf
Institutions: Erasmus MC, Rotterdam Study, Boston University, Framingham Heart Study, University of Washington, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, University of Minnesota, University of Vermont, National Institute on Aging, University of Arizona, University of North Carolina at Chapel Hill, University of Pittsburgh, Johns Hopkins University, University of California, Davis, Group Health Cooperative, VA Office of Research and Development, Seattle Epidemiologic Information and Research Center, Cedars-Sinai Medical Center, Elisabeth-TweeSteden Ziekenhuis, University of Mississippi Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Institutes of Health, U.S. Public Health Service, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: G1023702118, G118440752, G1194337659, G1220223050, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1325221871, G1332411685, UC Davis Alzheimer's Disease Core Center, G136105103, G1397335784, G1462415530, CHS-ULTRASOUND READING, CORONARY HEART DISEASE AND STROKE, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, G2078309758, Atherosclerosis Risk in Communities Study (ARIC), G215333750, G2194386449, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G232440474, G2391884931, Institute for Clinical and Translational Research (UL1), G250621538, CCSP FIELD CENTER, G25881238, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G270907595, G277826483, G278975345, G2800149121, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, G2818913090, G297113894, G3045517347, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3236609591, G328935669, G34347772, G36433118, G36937976, GWA for Gene-Environment Interaction Effects Influencing CHD, G390162502, G395403786, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4048755144, G412671775, G423252844, Atherosclerosis Risk in Communities Study (ARIC), G4617276643, G500195777, G5164707915, G528395701, G536099884, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5451084504, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G5558075022, Atherosclerosis Risk in Communities Study (ARIC), G581887176, CHS Events Follow-up Study, G6203107232, G6226795708, MRI, Genetics & Cognitive Precursors of AD and Dementia, The Framingham Heart Study, CHS-Transition Phase, G7176672723, CHS RETINAL READING CENTER, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G786153652, G793702358, G7999488110, G812579647, G8402048158, G8486527673, G8593276544, Diabetes Research Center (DRC), From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G931818222, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2011877873