Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms.
An intracranial aneurysm (IA), which results in a subarachnoid hemorrhage with a high mortality on rupture, is a major public health concern. To identify genetic susceptibility loci for IA, we carried out a multistage association study using genome-wide single nucleotide polymorphisms (SNPs) in Japanese case-control subjects. In this study, we assessed evidence for association in standard approaches, and additional tests with adjusting sex effects that act between genetic effect and disease. Consequently, five SNPs (P=1.31 × 10(-5) for rs1930095 of intergenic region; P=1.32 × 10(-5) for rs4628172 of TMEM195; P=2.78 × 10(-5) for rs7781293 of TMEM195; P=4.93 × 10(-5) for rs7550260 of ARHGEF11; and P=3.63 × 10(-5) for rs9864101 of IQSEC1) with probabilities of being false positives <0.5 were associated with IA in Japanese population, and the susceptibility genes could have a role in actin remodeling in the ELN/LIMK pathway. This study indicates the presence of several susceptibility loci that deserve further investigation in the Japanese population.
Akiyama
Koichi
K
Department of Molecular Life Sciences, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Narita
Akira
A
Nakaoka
Hirofumi
H
Cui
Tailin
T
Takahashi
Tomoko
T
Yasuno
Katsuhito
K
Tajima
Atsushi
A
Krischek
Boris
B
Yamamoto
Ken
K
Kasuya
Hidetoshi
H
Hata
Akira
A
Inoue
Ituro
I
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D016678:Genome; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide
D020662:Guanine Nucleotide Exchange Factors; C504483:IQSEC1 protein, human