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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article discusses a region on Chromosome 7 was associated with intracranial aneurysm (IA) in a Dutch discovery sample used in a genomewide association study (GWAS). This new finding was replicated in another Dutch sample (but not in a Finnish sample), and in a meta-analysis of previous samples.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EIschemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Genomics\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EIschemia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EJoseph P. Broderick, MD, University of Cincinnati, Cincinnati, Ohio, USA, reported that a region on Chromosome 7 was associated with intracranial aneurysm (IA) in a Dutch discovery sample used in a genomewide association study (GWAS). This new finding was replicated in another Dutch sample (but not in a Finnish sample), and in a meta-analysis of the samples conducted by Dr. Broderick and colleagues.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThere is substantial evidence for a genetic role in IA, and Dr. Broderick stated that this evidence is the strongest for any type of stroke. There is also genetic evidence for other Mendelian diseases associated with IA, such as polycystic kidney disease and Ehlers-Danlos. About 10% of patients with IA have a first-degree relative with a history of subarachnoid hemorrhage, and there is a high rate of intracranial hemorrhage amongst patients with familial IA (FIA). The location of IA is genetically mediated in FIA families and in twin studies. Prior GWAS studies have shown regional associations on chromosomes 4, 8, 9, 10, 12, 13, 18, and 20.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe Dutch discovery sample included 2644 white patients (male, 28%) from six different populations, and 2548 controls (male, 38%) from five different populations, including patients from the Atherosclerosis Risk in Communities study. The mean age of IA onset was 53.3 years in the discovery sample and 57.9 years in the control sample.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe GWAS of the Dutch discovery sample revealed two peaks; one at chromosome 9 and the other at chromosome 7. In the chromosome 9 region, the CDKN2BAS, or the ANRIL gene, is most pronounced, and the reason it causes an aneurysm is a matter of great discussion, said Dr. Broderick, even though this region has been linked to aneurysms in the brain and abdomen, and to myocardial infarction, among other outcomes, showing that there are many phenotypes within this region.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EFurther, there was an overlap between the location of the primary association for IA on chromosome 7 and that for ischemic stroke reported by Matarin and colleagues. The association for the former had genomewide significance, while the latter did not. Another overlap was found between a tertiary location found on chromosome 7 and that for \u003Cspan class=\u0022underline\u0022\u003Elarge vessel ischemic stroke that reached genomewide\u003C\/span\u003E significance [International Stroke Genetics Consortium. \u003Cem\u003ENat Genet\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EAlthough there was replication in the Dutch cohort, there was no replication in the Finnish cohort, although it was in the right direction, said Dr. Broderick, and there was genomewide significance in the meta-analysis.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe findings in this study may represent another overlap of a gene region associated with large vessel ischemic stroke and with IA, such as chromosome 9p21 - ANRIL, which has been clearly documented, said Dr. Broderick. This suggests that genetic risk factors associated with large vessel pathophysiology may present with different stroke phenotypes. More GWAS, exome sequencing, and functional studies are needed to further delineate the genetic underpinnings of IA.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/1\/18.2.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzpdkp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}