title: Association analyses confirming a susceptibility locus for intracranial aneurysm at chromosome 14q23.
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.
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mineharu
authors.affiliation: Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Neurosurgery, Yuri Kumiai General Hospital, Akita, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Neurosurgery, Senboku Kumiai General Hospital, Akita, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ohishi
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nozaki
authors.affiliation: Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan. koizumi@pbh.med.kyoto-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D002532:Intracranial Aneurysm / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics; D000071636:Protein Phosphatase 2C; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010749:Phosphoprotein Phosphatases; D011493:Protein Kinase C; D000071636:Protein Phosphatase 2C; D015534:Trans-Activators; D014157:Transcription Factors; C497442:HIF1A protein, human; C514215:MNAT1 protein, human; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C491945:SIX6 protein, human