title: Identification of SNP markers for common CNV regions and association analysis of risk of subarachnoid aneurysmal hemorrhage in Japanese population.
abstract: Copy number variation (CNV) is emerging as a new tool for understanding human genomic variation, but its relationship with human disease is not yet fully understood. The data for a total of 317,503 genotypes were collected for a genome-wide association study of subarachnoid aneurismal hemorrhage (SAH) in a Japanese population (cases and controls, n=497) using Illumina HumanHap300 BeadChip. To identify multi-allelic CNV markers, we visually inspected all genotype clusters of 317,503 SNP markers covering the whole genome using Illumina's BeadStudio 3.0 software. As a result, we identified 597 multi-allelic CNV markers for common (copy loss frequency>0.05) CNV regions in a Japanese population (n=497). The identified CNV markers shared the following characteristics: enrichment of Hardy-Weinberg disequilibria, Mendelian inconsistency among families, and high missing genotype rate. All annotated information for those markers is summarized in our database (http://www.snp-genetics.com/user/srch.htm). In addition, we performed case-control association analyses of identified multi-allelic CNV markers with the risk of subarachnoid aneurysmal hemorrhage. One SNP marker (rs1242541) within a CNV region neighboring the Sel-1 suppressor of lin-12-like protein (SEL1L) was significantly associated with a risk of SAH (P=0.0006). We also validated the CNV around rs1242541 using real-time quantitative polymerase chain reaction (PCR). Information and methods used in this study would be helpful for accurate genotyping of SNPs on CNV regions, which could be used for association analysis of SNP markers within CNV regions.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Room 1407, Complex B, WooLim Lion's Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul 153-801, Republic of Korea.
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Ji-On
authors.initials: JO
authors.lastname: Kim
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Sangsoo
authors.initials: S
authors.lastname: Kim
authors.forename: Ji-woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Tailin
authors.initials: T
authors.lastname: Cui
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D018628:Gene Dosage; D005819:Genetic Markers; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012306:Risk; D017422:Sequence Analysis, DNA / Q000379:methods; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D011506:Proteins; C117384:SEL1L protein, human