title: Associations between incident ischemic stroke events and stroke and cardiovascular disease-related genome-wide association studies single nucleotide polymorphisms in the Population Architecture Using Genomics and Epidemiology study.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored.
  
  
  RESULTS
  Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS.
  
  
  CONCLUSIONS
  Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.
authors.affiliation: Public Health Sciences, Fred Hutchinson Cancer Research Center. University of Washington, 1100 Fairview Ave N., Seattle, WA 98109, USA. ccarty@fhcrc.org
authors.forename: Cara L
authors.initials: CL
authors.lastname: Carty
authors.forename: Petra
authors.initials: P
authors.lastname: Buzková
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Shelley
authors.initials: S
authors.lastname: Cole
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Sue
authors.initials: S
authors.lastname: Mann
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tara C
authors.initials: TC
authors.lastname: Matise
authors.forename: Ross
authors.initials: R
authors.lastname: Prentice
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D005260:Female; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D044465:White People / Q000208:ethnology / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides