Three more risk loci for intracranial aneurysm reported
MedWire News: Researchers have identified three new genetic loci that contribute to people’s risk for developing intracranial aneurysms.
The study published in Nature Genetics also confirms the impact of two previously reported loci on intracranial aneurysm risk.
Given the size and power of the study, Murat Günel (Yale University School of Medicine, New Haven, Connecticut, USA) and colleagues say that “the evidence that these are bona fide risk loci for intracranial aneurysm is very strong.”
The team genotyped 2780 European patients with intracranial aneurysms and 12,515 controls for more than 800,000 single nucleotide polymorphisms (SNPs), revealing five loci that had strong associations with intracranial aneurysm.
Three of these were newly identified SNP clusters, located in the chromosomal regions 10q24.32, 13q13.1, and 18q11.2. The other two loci, on 8q11.23–q12.1 and 9p21.3, were reported by the team in a previous, smaller study. The third loci identified in that study – on 2q33 – did not associate with intracranial aneurysm in the current study, which was almost three times larger.
The five loci were successfully replicated in a Japanese cohort comprising 3111 cases and 1666 controls. However, the locus on 8q11.23–q12.1 contained two association signals in the original cohort, only one of which was significant in the replication cohort.
Günel and team say their new findings support their hypothesis that mutations in genes influencing cell cycle progression may affect intracranial aneurysm risk.
For example, the gene RBBP8, in the 18q11.2 region, encodes a protein that affects the cell cycle by interacting with the protein BRCA1, and overexpression of the protein encoded by the gene STARD13 in the 13q13.1 region causes suppression of cell proliferation.
The researchers estimate that the five currently identified SNPs explain between 3.5% and 5.2% of the familial risk for intracranial aneurysms.
“When combined with traditional risk factors such as gender, blood pressure, and smoking, these findings form the basis of future work aimed at preclinical identification of individuals who are at high risk for intracranial aneurysm formation and rupture,” they conclude.
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By Eleanor McDermid