Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

Debette, S; Bis, JC; Fornage, M; Schmidt, H; Ikram, MA; Sigurdsson, S; Heiss, G; Struchalin, M; Smith, AV; van der Lugt, A; Decarli, C; Lumley, T; Knopman, DS; Enzinger, C; Eiriksdottir, G; Koudstaal, PJ; Destefano, AL; Psaty, BM; Dufouil, C; Catellier, DJ; Fazekas, F; Aspelund, T; Aulchenko, YS; Beiser, A; Rotter, JI; Tzourio, C; Shibata, DK; Tscherner, M; Harris, TB; Rivadeneira, F; Atwood, LD; Rice, K; Gottesman, RF; van Buchem, MA; Uitterlinden, AG; Kelly-Hayes, M; Cushman, M; Zhu, Y; Boerwinkle, E; Gudnason, V; Hofman, A; Romero, JR; Lopez, O; van Duijn, CM; Au, R; Heckbert, SR; Wolf, PA; Mosley, TH; Seshadri, S; Breteler, MM; Schmidt, R; Launer, LJ; Longstreth, WT.
Genome-wide association studies of MRI-defined brain infarcts: meta-analysis from the CHARGE Consortium.
Stroke. 2010; 41(2): 210-217. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Enzinger Christian
Fazekas Franz
Schmidt Helena
Schmidt Reinhold
Tscherner Maria

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Number of Figures: 4
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BACKGROUND AND PURPOSE: Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed cross-sectional genome-wide association analysis of MRI infarct using age- and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance-weighted meta-analysis, including 9401 participants with mean age 69.7 (19.4% of whom had >or=1 MRI infarct). RESULTS: The most significant association was found with rs2208454 (minor allele frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI infarcts (odds ratio, 0.76; 95% confidence interval, 0.68-0.84; P=4.64x10(-7)). Highly suggestive associations (P<1.0x10(-5)) were also found for 22 other single nucleotide polymorphisms in linkage disequilibrium (r(2)>0.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 black participants, although 4 single nucleotide polymorphisms within 200 kb from rs2208454 were associated with MRI infarcts in the black population sample. CONCLUSIONS: This first community-based, genome-wide association study on covert MRI infarcts uncovered novel associations. Although replication of the association with top single nucleotide polymorphisms failed, possibly because of insufficient power, results in the black population sample are encouraging, and further efforts at replication are needed.
Find related publications in this database (using NLM MeSH Indexing)
African Americans - genetics
Aged -
Brain - pathology Brain - physiopathology
Brain Infarction - genetics Brain Infarction - pathology Brain Infarction - physiopathology
Cohort Studies -
DNA Mutational Analysis -
Female -
Gene Frequency - genetics
Genetic Markers - genetics
Genetic Predisposition to Disease - genetics
Genetic Testing -
Genetic Variation - genetics
Genome-Wide Association Study - statistics and numerical data
Humans -
Linkage Disequilibrium - genetics
Magnetic Resonance Imaging -
Male -
Middle Aged -
Polymorphism, Single Nucleotide - genetics
Prospective Studies -

Find related publications in this database (Keywords)
brain infarction
cohort study
genome-wide association study
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