Genome-wide association analysis of ischemic stroke in young adults

Yu Ching Cheng, Jeffrey R. O'Connell, John W. Cole, O. Colin Stine, Nicole Dueker, Patrick F. McArdle, Mary J. Sparks, Jess Shen, Cathy C. Laurie, Sarah Nelson, Kimberly F. Doheny, Hua Ling, Elizabeth W. Pugh, Thomas G. Brott, Robert D. Brown, James F. Meschia, Michael Nalls, Stephen S. Rich, Bradford Worrall, Christopher D. AndersonAlessandro Biffi, Lynelle Cortellini, Karen L. Furie, Natalia S. Rost, Jonathan Rosand, Teri A. Manolio, Steven J. Kittner, Braxton D. Mitchell

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15-49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P <5 × 10-8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P 1/4 1.2 × 10-7) and rs1986743 (in ARL6IP6; P 1/4 2.7 × 10-7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalG3: Genes, Genomes, Genetics
Volume1
Issue number6
DOIs
StatePublished - Nov 1 2011

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Keywords

  • Brain infarction
  • Epidemiology
  • FMNL2
  • Genetics

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Cheng, Y. C., O'Connell, J. R., Cole, J. W., Colin Stine, O., Dueker, N., McArdle, P. F., Sparks, M. J., Shen, J., Laurie, C. C., Nelson, S., Doheny, K. F., Ling, H., Pugh, E. W., Brott, T. G., Brown, R. D., Meschia, J. F., Nalls, M., Rich, S. S., Worrall, B., ... Mitchell, B. D. (2011). Genome-wide association analysis of ischemic stroke in young adults. G3: Genes, Genomes, Genetics, 1(6), 505-514. https://doi.org/10.1534/g3.111.001164