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Genomewide association studies of stroke.
Tuesday,2012-11-06 12:10 America/Los_Angeles — eenright
| Title | Genomewide association studies of stroke. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Ikram, AM, Seshadri, S, Bis, JC, Fornage, M, DeStefano, AL, Aulchenko, YS, Debette, S, Lumley, T, Folsom, AR, van den Herik, EG, Bos, MJ, Beiser, A, Cushman, M, Launer, LJ, Shahar, E, Struchalin, M, Du, Y, Glazer, NL, Rosamond, WD, Rivadeneira, F, Kelly-Hayes, M, Lopez, OL, Coresh, J, Hofman, A, DeCarli, C, Heckbert, SR, Koudstaal, PJ, Yang, Q, Smith, NL, Kase, CS, Rice, K, Haritunians, T, Roks, G, de Kort, PLM, Taylor, KD, de Lau, LM, Oostra, BA, Uitterlinden, AG, Rotter, JI, Boerwinkle, E, Psaty, BM, Mosley, TH, van Duijn, CM, Breteler, MMB, Longstreth, WT, Wolf, PA |
| Journal | N Engl J Med |
| Volume | 360 |
| Issue | 17 |
| Pagination | 1718-28 |
| Date Published | 2009 Apr 23 |
| ISSN | 1533-4406 |
| Keywords | African Continental Ancestry Group, Aged, Chromosomes, Human, Pair 12, Cohort Studies, European Continental Ancestry Group, Female, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors, Stroke |
| Abstract | <p><b>BACKGROUND: </b>The genes underlying the risk of stroke in the general population remain undetermined.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>A genetic locus on chromosome 12p13 is associated with an increased risk of stroke.</p> |
| DOI | 10.1056/NEJMoa0900094 |
| Alternate Journal | N Engl J Med |
| PubMed ID | 19369658 |
| PubMed Central ID | PMC2768348 |
| Grant List | R01HL59367 / HL / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States AG08122 / AG / NIA NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States M01RR00069 / RR / NCRR NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States AG16495 / AG / NIA NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States |