title: Structural genomic variation in ischemic stroke.
abstract: Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions; 3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study.
authors.affiliation: Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mar
authors.initials: M
authors.lastname: Matarin
authors.forename: Javier
authors.initials: J
authors.lastname: Simon-Sanchez
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Sonja
authors.initials: S
authors.lastname: Scholz
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Cynthia
authors.initials: C
authors.lastname: Crews
authors.forename: Angela
authors.initials: A
authors.lastname: Britton
authors.forename: Fabienne Wavrant
authors.initials: FW
authors.lastname: De Vrieze
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Brott
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brown
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.forename: Scott
authors.initials: S
authors.lastname: Silliman
authors.forename: L Douglas
authors.initials: LD
authors.lastname: Case
authors.forename: John A
authors.initials: JA
authors.lastname: Hardy
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*; D044465:White People / Q000235:genetics