03465nas a2200745 4500000000100000008004100001653001000042653001100052653001100063653000900074653000900083653001600092653001900108653004100127653005000168653004300218653004600261653004600307100001700353700001100370700001500381700001600396700001400412700001400426700001400440700001400454700001000468700001500478700001400493700001500507700001600522700001700538700001900555700001100574700001700585700001300602700001700615700001600632700001600648700002100664700001200685700001400697700001900711700002000730700001600750700001700766700001900783700001300802700001400815700001500829700001500844700001500859700001200874700001400886700001300900700001500913700001400928700001700942245010400959250001501063300001101078490000701089520157201096020005102668 2014 d 10 aAdult 10 aFemale 10 aHumans 10 aAged 10 aMale 10 aMiddle Aged 10 aCohort Studies 10 aChromosomes, Human, Pair 7/ genetics 10 aEuropean Continental Ancestry Group/ genetics 10 aGenome-Wide Association Study/ methods 10 aIntracranial Aneurysm/diagnosis/ genetics 10 aPolymorphism, Single Nucleotide/ genetics 1 aSauerbeck L. 1 aWoo D. 1 aRouleau G. 1 aMeissner I. 1 aForoud T. 1 aMackey J. 1 aMoomaw C. 1 aKoller D. 1 aKo N. 1 aFornage M. 1 aHuston J. 1 aWorrall B. 1 aEriksson J. 1 aBroderick J. 1 aAnderson Craig 1 aLai D. 1 aF. Hof Van't 1 aKurki M. 1 aBrown R. Jr. 1 aConnolly E. 1 aFlaherty M. 1 aM. Fraunberg von 1 aGaal E. 1 aLaakso A. 1 aHernesniemi J. 1 aJaaskelainen J. 1 aKiemeney L. 1 aKivisaari R. 1 aKleindorfer D. 1 aLehto H. 1 aMosley T. 1 aMoskala M. 1 aNiemela M. 1 aPalotie A. 1 aPera J. 1 aRinkel G. 1 aRipke S. 1 aRuigrok Y. 1 aSlowik A. 1 aVermeulen S. 00 aGenome-wide association study of intracranial aneurysm identifies a new association on chromosome 7 a2014/09/27 a3194-9 0 v45 3 a
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.
a1524-4628 (Electronic)
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