title: Differential effects of chromosome 9p21 variation on subphenotypes of intracranial aneurysm: site distribution.
abstract: OBJECTIVE
  Recently, a genome-wide association study identified associations between single nucleotide polymorphisms on chromosome 9p21 and risk of harboring intracranial aneurysm (IA). Aneurysm characteristics or subphenotypes of IAs, such as history of subarachnoid hemorrhage, presence of multiple IAs and location of IAs, are clinically important. We investigated whether the association between 9p21 variation and risk of IA varied among these subphenotypes.
  
  
  METHODS
  We conducted a case-control study of 981 cases and 699 controls in Japanese. Four single nucleotide polymorphisms tagging the 9p21 risk locus were genotyped. The OR and 95% CI were estimated using logistic regression analyses.
  
  
  RESULTS
  Among the 4 single nucleotide polymorphisms, rs1333040 showed the strongest evidence of association with IA (P=1.5x10(-6); per allele OR, 1.43; 95% CI, 1.24-1.66). None of the patient characteristics (gender, age, smoking, and hypertension) was a significant confounder or effect modifier of the association. Subgroup analyses of IA subphenotypes showed that among the most common sites of IAs, the association was strongest for IAs of the posterior communicating artery (OR, 1.69; 95% CI, 1.26-2.26) and not significant for IAs in the anterior communicating artery (OR, 1.22; 95% CI, 0.96-1.57). When dichotomizing IA sites, the association was stronger for IAs of the posterior circulation-posterior communicating artery group (OR, 1.73; 95% CI, 1.32-2.26) vs the anterior circulation group (OR, 1.28; 95% CI, 1.07-1.53). Heterogeneity in these ORs was significant (P=0.032). The associations did not vary when stratifying by history of subarachnoid hemorrhage (OR, 1.42; 95% CI, 1.18-1.71 for ruptured IA; OR, 1.27; 95% CI, 1.00-1.62 for unruptured IA) or by multiplicity of IA (OR, 1.57; 95% CI, 1.21-2.03 for multiple IAs; OR, 1.36; 95% CI, 1.15-1.61 for single IA).
  
  
  CONCLUSIONS
  Our results suggest that genetic influence on formation may vary between IA subphenotypes.
authors.affiliation: Division of Molecular Life Science, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakaoka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Akiyama
authors.forename: Tailin
authors.initials: T
authors.lastname: Cui
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tajima
authors.forename: Boris
authors.initials: B
authors.lastname: Krischek
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kasuya
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017542:Aneurysm, Ruptured / Q000145:classification / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics; D002532:Intracranial Aneurysm / Q000145:classification / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics