@article{21236, keywords = {Adult, Female, Humans, Aged, Male, Middle Aged, Cohort Studies, Chromosomes, Human, Pair 7/ genetics, European Continental Ancestry Group/ genetics, Genome-Wide Association Study/ methods, Intracranial Aneurysm/diagnosis/ genetics, Polymorphism, Single Nucleotide/ genetics}, author = {Sauerbeck L. and Woo D. and Rouleau G. and Meissner I. and Foroud T. and Mackey J. and Moomaw C. and Koller D. and Ko N. and Fornage M. and Huston J. and Worrall B. and Eriksson J. and Broderick J. and Anderson Craig and Lai D. and F. Hof Van't and Kurki M. and Brown R. Jr. and Connolly E. and Flaherty M. and M. Fraunberg von and Gaal E. and Laakso A. and Hernesniemi J. and Jaaskelainen J. and Kiemeney L. and Kivisaari R. and Kleindorfer D. and Lehto H. and Mosley T. and Moskala M. and Niemela M. and Palotie A. and Pera J. and Rinkel G. and Ripke S. and Ruigrok Y. and Slowik A. and Vermeulen S.}, title = {Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7}, abstract = {

BACKGROUND AND PURPOSE: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. METHODS: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. RESULTS: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0x10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14x10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91x10(-10)). CONCLUSIONS: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.

}, year = {2014}, journal = {Stroke}, volume = {45}, edition = {2014/09/27}, number = {11}, pages = {3194-9}, isbn = {1524-4628 (Electronic)
0039-2499 (Linking)}, note = {Foroud, Tatiana
Lai, Dongbing
Koller, Daniel
Van't Hof, Femke
Kurki, Mitja I
Anderson, Craig S
Brown, Robert D Jr
Connolly, Edward Sander
Eriksson, Johan G
Flaherty, Matthew
Fornage, Myriam
von Und Zu Fraunberg, Mikael
Gaal, Emilia I
Laakso, Aki
Hernesniemi, Juha
Huston, John
Jaaskelainen, Juha E
Kiemeney, Lambertus A
Kivisaari, Riku
Kleindorfer, Dawn
Ko, Nerissa
Lehto, Hanna
Mackey, Jason
Meissner, Irene
Moomaw, Charles J
Mosley, Thomas H
Moskala, Marek
Niemela, Mika
Palotie, Aarno
Pera, Joanna
Rinkel, Gabriel
Ripke, Stephan
Rouleau, Guy
Ruigrok, Ynte
Sauerbeck, Laura
Slowik, Agnieszka
Vermeulen, Sita H
Woo, Daniel
Worrall, Bradford B
Broderick, Joseph
Familial Intracranial Aneurysm Study Investigators
HHSN268200625226C/PHS HHS/United States
HHSN268201100005C/PHS HHS/United States
HHSN268201100006C/PHS HHS/United States
HHSN268201100007C/PHS HHS/United States
HHSN268201100008C/PHS HHS/United States
HHSN268201100009C/PHS HHS/United States
HHSN268201100010C/PHS HHS/United States
HHSN268201100011C/PHS HHS/United States
HHSN268201100012C/PHS HHS/United States
HL096814/HL/NHLBI NIH HHS/United States
HL096899/HL/NHLBI NIH HHS/United States
HL096902/HL/NHLBI NIH HHS/United States
HL096917/HL/NHLBI NIH HHS/United States
R01 NS039512/NS/NINDS NIH HHS/United States
R01-HL70825/HL/NHLBI NIH HHS/United States
R01HL086694/HL/NHLBI NIH HHS/United States
R01HL087641/HL/NHLBI NIH HHS/United States
R01HL59367/HL/NHLBI NIH HHS/United States
R01NS39512/NS/NINDS NIH HHS/United States
R03NS083468/NS/NINDS NIH HHS/United States
U01 HL096812/HL/NHLBI NIH HHS/United States
U01HG004402/HG/NHGRI NIH HHS/United States
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
Stroke. 2014 Nov;45(11):3194-9. doi: 10.1161/STROKEAHA.114.006096. Epub 2014 Sep 25.}, language = {eng}, }