Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11

Am J Hum Genet. 2001 Oct;69(4):804-19. doi: 10.1086/323614. Epub 2001 Aug 28.


Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the genetic determinants. We report here a genomewide linkage study of IA in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for IA. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81x10-6), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39. These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alleles
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7 / genetics*
  • Exons / genetics
  • Female
  • Gene Frequency / genetics
  • Genetic Linkage / genetics*
  • Genome, Human
  • Haplotypes / genetics*
  • Heterozygote
  • Humans
  • Intracranial Aneurysm / diagnostic imaging
  • Intracranial Aneurysm / genetics*
  • Intracranial Aneurysm / pathology
  • Introns / genetics
  • Linkage Disequilibrium / genetics
  • Male
  • Matched-Pair Analysis
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense / genetics
  • Nuclear Family
  • Physical Chromosome Mapping
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • Radiography


  • 3' Untranslated Regions

Associated data

  • GENBANK/AC005056
  • GENBANK/AC005057
  • GENBANK/AC005081
  • GENBANK/AC005089
  • GENBANK/AF045555
  • GENBANK/M36860
  • GENBANK/U62292
  • GENBANK/U62293
  • GENBANK/U63721
  • GENBANK/U93037
  • OMIM/105800