DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Intracranial aneurysm. The EFO term brain aneurysm was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: brain aneurysm

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

SK Low, A Takahashi, PC Cha, H Zembutsu, N Kamatani, M Kubo, Y Nakamura

TITLE:

Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA.

JOURNAL:

Human molecular genetics May 2012, Vol 21, pp. 2102-10

ABSTRACT:

Aneurysmal subarachnoid hemorrhage (aSAH) is the most serious subtype of stroke. Genetic factors have been known to play an important role in the development of intracranial aneurysm (IA), some of which further progress to subarachnoid hemorrhage (SAH). In this study, we conducted a genome-wide association study (GWAS) to identify common genetic variants that are associated with the risk of IA, using 1383 aSAH subjects and 5484 control individuals in the Japanese population. We selected 36 single-nucleotide polymorphisms (SNPs) that showed suggestive association (P <1 × 10(-4)) in the GWAS as well as additional 7 SNPs that were previously reported to be associated with IA, and further genotyped an additional set of 1048 IA cases and 7212 controls. We identified an SNP, rs6842241, near EDNRA at chromosome 4q31.22 (combined P-value = 9.58 × 10(-9); odds ratio = 1.25), which was found to be significantly associated with IA. Additionally, we successfully replicated and validated rs10757272 on CDKN2BAS at chromosome 9p21.3 (combined P-value = 1.55 × 10(-7); odds ratio = 1.21) to be significantly associated with IA as previously reported. Furthermore, we performed functional analysis with the associated genetic variants on EDNRA, and identified two alleles of rs6841581 that have different binding affinities to a nuclear protein(s). The transcriptional activity of the susceptible allele of this variant was significantly lower than the other, suggesting that this functional variant might affect the expression of EDNRA and subsequently result in the IA susceptibility. Identification of genetic variants on EDNRA is of clinical significance probably due to its role in vessel hemodynamic stress. Our findings should contribute to a better understanding of physiopathology of IA. PUBMED: 22286173
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