Association analyses confirming a susceptibility locus for intracranial aneurysm at chromosome 14q23.
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.
Mineharu
Yohei
Y
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.
Inoue
Kayoko
K
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
Inoue
Sumiko
S
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Konoe-cho, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
Kikuchi
Kenji
K
Department of Neurosurgery, Yuri Kumiai General Hospital, Akita, Japan.
Ohishi
Hikaru
H
Department of Neurosurgery, Senboku Kumiai General Hospital, Akita, Japan.
Nozaki
Kazuhiko
K
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hashimoto
Nobuo
N
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Koizumi
Akio
A
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.
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
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