Combination of linkage and association studies for brain arteriovenous malformation.
OBJECTIVE
Genetic factors for brain arteriovenous malformation are unexplored because of the low incidence of familial cases, albeit local and familial clustering. We used a combination of a linkage study and an association study to explore the genetic background.


METHODS
A genome-wide linkage analysis was performed in 12 patients from 6 unrelated families using the GENEHUNTER program. A genome-wide association analysis of 26 cases and 30 controls was performed using a GeneChip 10K mapping array. Significance levels for linkage and single single-nucleotide polymorphism association analyses were set at P<0.05 and P<0.0001, respectively. Genotyping was also performed using 58 960 single-nucleotide polymorphisms for 2 sets of discordant twins.


RESULTS
The linkage analysis revealed 7 candidate regions, with the highest logarithm of odds score of 1.88 (P=0.002) at chromosome 6q25. A significant association was observed for 4 single-nucleotide polymorphisms and 2 haplotypes, but none of them overlapped with candidate linkage regions. Genotyping of the twins showed no genetic heterogeneity.


CONCLUSIONS
The present study failed to identify genetic factors for arteriovenous malformation although the low statistical power may have resulted in such evidence being missed.
Inoue
Sumiko
S
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, Japan.
Liu
Wanyang
W
Inoue
Kayoko
K
Mineharu
Youhei
Y
Takenaka
Katsunobu
K
Yamakawa
Hiroyasu
H
Abe
Masamitsu
M
Jafar
Jafar J
JJ
Herzig
Roman
R
Koizumi
Akio
A
D000328:Adult; D002874:Chromosome Mapping / Q000379:methods*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D016678:Genome / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics* / Q000503:physiopathology; D007564:Japan; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics