TY - JOUR
T1 - Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms
AU - Akiyama, Koichi
AU - Narita, Akira
AU - Nakaoka, Hirofumi
AU - Cui, Tailin
AU - Takahashi, Tomoko
AU - Yasuno, Katsuhito
AU - Tajima, Atsushi
AU - Krischek, Boris
AU - Yamamoto, Ken
AU - Kasuya, Hidetoshi
AU - Hata, Akira
AU - Inoue, Ituro
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
KW - cerebrovascular disease
KW - genetics
KW - genome-wide association study
KW - intracranial aneurysm
KW - sex effect
KW - single nucleotide polymorphism
KW - subarachnoid hemorrhage
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U2 - 10.1038/jhg.2010.82
DO - 10.1038/jhg.2010.82
M3 - Article
C2 - 20613766
AN - SCOPUS:78049254965
SN - 1434-5161
VL - 55
SP - 656
EP - 661
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 10
ER -
