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

Authors:
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, Jürgen Beck, Teresa Sola, Filomena Ricciardi, Arpo Aromaa, Thomas Illig, Stefan Schreiber, Cornelia M van Duijn, Leonard H van den Berg, Claire Perret, Carole Proust, Constantin Roder, Ali K Ozturk, Emília Gaál, Daniela Berg, Christof Geisen, Christoph M Friedrich, Paul Summers, Alejandro F Frangi, Matthew W State, H Erich Wichmann, Monique M B Breteler, Cisca Wijmenga, Shrikant Mane, Leena Peltonen, Vivas Elio, Miriam C J M Sturkenboom, Patricia Lawford, James Byrne, Juan Macho, Erol I Sandalcioglu, Bernhard Meyer, Andreas Raabe, Helmuth Steinmetz, Daniel Rüfenacht, Juha E Jääskeläinen, Juha Hernesniemi, Gabriel J E Rinkel, Hitoshi Zembutsu, Ituro Inoue, Aarno Palotie, François Cambien, Yusuke Nakamura, Richard P Lifton, Murat Günel
Year of publication:
2010
Volume:
42
Issue:
5
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
Abstract: 
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.