Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11.
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.
Onda
H
H
Department of Neurosurgry, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan.
Kasuya
H
H
Yoneyama
T
T
Takakura
K
K
Hori
T
T
Takeda
J
J
Nakajima
T
T
Inoue
I
I
D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D009679:Nuclear Family; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011859:Radiography
D020413:3' Untranslated Regions