title: Whole Blood Gene Expression Profiles of Patients with a Past Aneurysmal Subarachnoid Hemorrhage.
abstract: BACKGROUND
  The pathogenesis of development and rupture of intracranial aneurysms (IA) is largely unknown. Also, screening for IA to prevent aneurysmal subarachnoid hemorrhage (aSAH) is inefficient, as disease markers are lacking. We investigated gene expression profiles in blood of previous aSAH patients, who are still at risk for future IA, aiming to gain insight into the pathogenesis of IA and aSAH, and to make a first step towards improvement of aSAH risk prediction.
  
  
  RESULTS
  We collected peripheral blood of 119 patients with aSAH at least two years prior, and 118 controls. We determined gene expression profiles using Illumina HumanHT-12v4 BeadChips. After quality control, we divided the dataset in a discovery (2/3) and replication set (1/3), identified differentially expressed genes, and applied (co-)differential co-expression to identify disease-related gene networks. No genes with a significant (false-discovery rate <5%) differential expression were observed. We detected one gene network with significant differential co-expression, but did not find biologically meaningful gene networks related to a history of aSAH. Next, we applied prediction analysis of microarrays to find a gene set that optimally predicts absence or presence of a history of aSAH. We found no gene sets with a correct disease state prediction higher than 40%.
  
  
  CONCLUSIONS
  No gene expression differences were present in blood of previous aSAH patients compared to controls, besides one differentially co-expressed gene network without a clear relevant biological function. Our findings suggest that gene expression profiles, as detected in blood of previous aSAH patients, do not reveal the pathogenesis of IA and aSAH, and cannot be used for aSAH risk prediction.
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Femke N G
authors.initials: FN
authors.lastname: van 't Hof
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ynte M
authors.initials: YM
authors.lastname: Ruigrok
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jelena
authors.initials: J
authors.lastname: Medic
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Bahram
authors.initials: B
authors.lastname: Sanjabi
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Vlies
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017542:Aneurysm, Ruptured / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000235:genetics*; D059467:Transcriptome; D055815:Young Adult