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

Katsuhito Yasuno, Kaya Bilguvar, Philippe Bijlenga, Siew-Kee Low, Boris Krischek, Georg Auburger, Matthias Simon, Dietmar Krex, Zulfikar Arlier, Nikhil Nayak, Ynte M Ruigrok, Mika Niemelä, Atsushi Tajima, Mikael von und zu Fraunberg, Tamás Dóczi, Florentina Wirjatijasa, Akira Hata, Jordi Blasco, Agi Oszvald, Hidetoshi Kasuya, Gulam Zilani, Beate Schoch, Pankaj Singh, Carsten Stüer, Roelof Risselada et al.

Nature Genetics (2010) doi:10.1038/ng.563

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 ~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 × 10−12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10−9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10−9). We also confirmed prior associations near SOX17 (8q11.23–q12.1; OR = 1.28, P = 1.3 × 10−12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 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.