Genetic variation contributes to gene expression response in ischemic stroke: an eQTL study

Hajar Amini, Natasha Shroff, Boryana Stamova, Eva Ferino, Paulina Carmona-Mora, Xinhua Zhan, Preston P. Sitorus, Heather Hull, Glen Clifford Jickling, Frank R. Sharp, Bradley P. Ander

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: Single nucleotide polymorphisms (SNPs) contribute to complex disorders such as ischemic stroke (IS). Since SNPs could affect IS by altering gene expression, we studied the association of common SNPs with changes in mRNA expression (i.e. expression quantitative trait loci; eQTL) in blood after IS. Methods: RNA and DNA were isolated from 137 patients with acute IS and 138 vascular risk factor controls (VRFC). Gene expression was measured using Affymetrix HTA 2.0 microarrays and SNP variants were assessed with Axiom Biobank Genotyping microarrays. A linear model with a genotype (SNP) × diagnosis (IS and VRFC) interaction term was fit for each SNP-gene pair. Results: The eQTL interaction analysis revealed significant genotype × diagnosis interaction for four SNP-gene pairs as cis-eQTL and 70 SNP-gene pairs as trans-eQTL. Cis-eQTL involved in the inflammatory response to IS included rs56348411 which correlated with neurogranin expression (NRGN), rs78046578 which correlated with CXCL10 expression, rs975903 which correlated with SMAD4 expression, and rs62299879 which correlated with CD38 expression. These four genes are important in regulating inflammatory response and BBB stabilization. SNP rs148791848 was a strong trans-eQTL for anosmin-1 (ANOS1) which is involved in neural cell adhesion and axonal migration and may be important after stroke. Interpretation: This study highlights the contribution of genetic variation to regulating gene expression following IS. Specific inflammatory response to stroke is at least partially influenced by genetic variation. This has implications for progressing toward personalized treatment strategies. Additional research is required to investigate these genes as therapeutic targets.

Original languageEnglish (US)
JournalAnnals of Clinical and Translational Neurology
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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