Abstract
Previous linkage analyses of intracranial aneurysm (IA) have proposed several genetic susceptibility loci; however, some loci remain contradictory. The objective of this study was to confirm these loci in a Japanese population using allelic and haplotype association analyses. We set high-density single nucleotide polymorphism markers in previously suggested IA loci and conducted an association analysis in 29 cases and 35 controls from a small community in Akita, Japan. Genotyping was carried out using the GeneChip 10 K mapping array, and the association analysis was performed using GeneSpring GT2 software. The result was confirmed in a replication cohort consisting of 237 cases and 253 controls from all over Japan. Only one variant, rs767603, at chromosome 14q23, was significantly associated with IA, both in allelic analysis (p = 0.00017, Bonferroni-corrected p = 0.021) and haplotype analysis (p = 0.00178, Bonferroni-corrected p = 0.048). This association was confirmed in the replication cohort (p = 0.0046 for allelic association, p = 0.0060 for haplotype association). Our findings confirm 14q23 to be a susceptibility locus for intracranial aneurysm.
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Acknowledgments
This work was supported by a grant from the Ministry of Education, Science, Sports, and Culture of Japan to AK (Tokutei Kenkyu: 15012231, 16012232, 17019034 and 18018022) and a grant from the Japan Society for the Promotion of Science to AK (Kiban Kenkyu A: 14207016 and S: 17109007). YM is a Research Fellow (18–2738) of the Japan Society for the Promotion of Science. We thank Norio Matsuura, and Eriko Mori for technical assistance, and the following doctors for patient recruitment and help in ascertaining MRA examinations: Shinsuke Tominaga, Hiroshi Hasegawa, and Toshihiko Inui (Tominaga Hospital), Shyunichi Yoneda and Yoshito Naruo (Nihonbashi Hospital), Yoo Kang (Ohno Kinen Hospital), Hiroyasu Yamakawa (Gero-spring Hospital), Atsushi Kawarazaki (Kawarazaki Hospital), Masayuki Matsuda (Shiga University of Medical Science), Michiyasu Suzuki and Sadahiro Nomura (Yamaguchi University School of Medicine), Takaaki Kaneko and Takuya Moriwaki (Hikone Municipal Hospital), Nozomu Murai (Otowa Hospital), Tomoo Tokime, Shoichi Tani and Susumu Kanemoto (Tenri Hospital), Tatsuhito Yamagami (Kyoto Kizugawa Hospital), Motoharu Fujii (International University of Health and Welfare), Hikaru Ohishi and Kiminari Ohtaka, Junko Sasaki, Koki Iwaya, and Masaya Iwakawa (Senboku Kumiai Sougou Hospital), Kenji Kikuchi and Yutaka Yamazaki (Yuri Kumiai Sougou Hospital), Shiro Nagasawa and Nobuhisa Mabuchi (Soseikai General Hospital), Yasuhiko Tokuriki (Fukui Red Cross Hospital), Sen Yamagata (Kurashiki Central Hospital), Kenji Hashimoto (Hyogo Prefectural Tsukaguchi Hospital), Atsushi Okumura (Takeda Hospital) Yoshihiko Uemura (Kyoto City Hospital), Kiyohiro Houkin and Osamu Honmou (Sapporo Medical University School of Medicine), Izumi Nagata (Nagasaki University School of Medicine), Ichiro Nakahara and Toshio Higashi (Kokura Memorial Hospital), and Takashi Yoshizawa and Kenjiro Ito (Yokohama Shintoshi Neurosurgical Hospital), Shigeki Yamada (Shiga Medical Center for Adults), Jun Takahashi, Nobuhiro Mikuni, Ken-ichiro Kikuta, Yasushi Takagi, and Yo Kishi (Kyoto University Graduate School of Medicine).
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Mineharu, Y., Inoue, K., Inoue, S. et al. Association analyses confirming a susceptibility locus for intracranial aneurysm at chromosome 14q23. J Hum Genet 53, 325–332 (2008). https://doi.org/10.1007/s10038-008-0255-5
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DOI: https://doi.org/10.1007/s10038-008-0255-5
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