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Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.

TitleGenome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.
Publication TypeJournal Article
Year of Publication2014
AuthorsForoud T, Lai D, Koller D, Hof FVan't, Kurki MI, Anderson CS, Brown RD, Connolly ESander, Eriksson JG, Flaherty M, Fornage M, Fraunberg Mvon Und Zu, Gaál EI, Laakso A, Hernesniemi J, Huston J, Jääskeläinen JE, Kiemeney LA, Kivisaari R, Kleindorfer D, Ko N, Lehto H, Mackey J, Meissner I, Moomaw CJ, Mosley TH, Moskala M, Niemelä M, Palotie A, Pera J, Rinkel G, Ripke S, Rouleau G, Ruigrok Y, Sauerbeck L, Słowik A, Vermeulen SH, Woo D, Worrall BB
Secondary AuthorsBroderick J
Corporate AuthorsFamilial Intracranial Aneurysm Study Investigators
JournalStroke
Volume45
Issue11
Pagination3194-9
Date Published2014 Nov
ISSN1524-4628
KeywordsAdult, Aged, Chromosomes, Human, Pair 7, Cohort Studies, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Intracranial Aneurysm, Male, Middle Aged, Polymorphism, Single Nucleotide
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

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.

DOI10.1161/STROKEAHA.114.006096
Alternate JournalStroke
PubMed ID25256182
PubMed Central IDPMC4213281
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HL096899 / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HL096902 / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HL096917 / HL / NHLBI NIH HHS / United States
R01 NS039512 / NS / NINDS NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
UL1 TR001108 / TR / NCATS NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
R01-HL70825 / HL / NHLBI NIH HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HL096814 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R03NS083468 / NS / NINDS NIH HHS / United States
R03 NS083468 / NS / NINDS NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
UL1 TR001425 / TR / NCATS NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01NS39512 / NS / NINDS NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
U01 NS036695 / NS / NINDS NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States