Genome-wide association study of intracranial aneurysm identifies three new risk loci.

Nat Genet 2010 May 4;42(5):420-5. Epub 2010 Apr 4.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861730PMC
May 2010
119 Reads
72 Citations
29.352 Impact Factor

Publication Analysis

Top Keywords

association study
8
intracranial aneurysms
8
genome-wide association
8
rbbp8 18q112
4
18q112 odds
4
intervals rbbp8
4
including intervals
4
odds ratio
4
dataset including
4
122 10-12
4
120 10-9
4
10-9 gene-rich
4
13q131 120
4
stard13-kl 13q131
4
combined dataset
4
10-12 stard13-kl
4
ratio 122
4
evidence association
4
imputed snps
4
snps discovery
4

Similar Publications