Abstract
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.
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Acknowledgements
We are grateful to the DNA donors and the supporting staffs for making this study possible. We thank Dr Hiroyuki Akagawa for his assistance with DNA specimen management. We also thank Makiko Funamizu, Midori Yamamoto, Kayako Fukuyama, Kozue Otaka, Eriko Tokubo, Hiromi Kamura and Miho Takabe for their technical help. This work was supported in part by CREST (Core Research for Evolutionary Science and Technology) of Japan Science and Technology (II) and a Grant-in-Aid for scientific research on Priority Area ‘Applied Genomics’ from the Japanese Ministry of Education, Science, Sports and Culture (II).
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Akiyama, K., Narita, A., Nakaoka, H. et al. Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms. J Hum Genet 55, 656–661 (2010). https://doi.org/10.1038/jhg.2010.82
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DOI: https://doi.org/10.1038/jhg.2010.82
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