Genome-Wide Association Study of Intracranial Aneurysm Identifies a New Association on Chromosome 7
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. Initial analysis was performed i...
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| creator | FOROUD, Tatiana DONGBING LAI FORNAGE, Myriam VON UND ZU FRAUNBERG, Mikael GAAL, Emília I LAAKSO, Aki HERNESNIEMI, Juha HUSTON, John JÄÄSKELÄINEN, Juha E KIEMENEY, Lambertus A KIVISAARI, Riku KLEINDORFER, Dawn KOLLER, Daniel KO, Nerissa LEHTO, Hanna MACKEY, Jason MEISSNER, Irene MOOMAW, Charles J MOSLEY, Thomas H MOSKALA, Marek NIEMELÄ, Mika PALOTIE, Aarno PERA, Joanna VAN'T HOF, Femke RINKEL, Gabriel RIPKE, Stephan ROULEAU, Guy RUIGROK, Ynte SAUERBECK, Laura SLOWIK, Agnieszka VERMEULEN, Sita H WOO, Daniel WORRALL, Bradford B BRODERICK, Joseph KURKI, Mitja I ANDERSON, Craig S BROWN, Robert D CONNOLLY, Edward Sander ERIKSSON, Johan G FLAHERTY, Matthew |
| description | 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.
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.
Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P |
| doi_str_mv | 10.1161/strokeaha.114.006096 |
| format | Article |
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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.
Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-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=9.91×10(-10)).
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.</description><identifier>ISSN: 0039-2499</identifier><identifier>ISSN: 1524-4628</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/strokeaha.114.006096</identifier><identifier>PMID: 25256182</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Chromosomes, Human, Pair 7 - genetics ; Cohort Studies ; Diseases of the nervous system ; Female ; Genome-Wide Association Study - methods ; Humans ; Intracranial Aneurysm - diagnosis ; Intracranial Aneurysm - genetics ; Male ; Medical sciences ; Middle Aged ; Neurology ; Polymorphism, Single Nucleotide - genetics ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Vascular diseases and vascular malformations of the nervous system ; White People - genetics</subject><ispartof>Stroke (1970), 2014-11, Vol.45 (11), p.3194-3199</ispartof><rights>2015 INIST-CNRS</rights><rights>2014 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-85a45b1fc77e719fd83e48bce71c8b1b5a475e0144890c22976e9926b4a5de613</citedby><cites>FETCH-LOGICAL-c504t-85a45b1fc77e719fd83e48bce71c8b1b5a475e0144890c22976e9926b4a5de613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28961067$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25256182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FOROUD, Tatiana</creatorcontrib><creatorcontrib>DONGBING LAI</creatorcontrib><creatorcontrib>FORNAGE, Myriam</creatorcontrib><creatorcontrib>VON UND ZU FRAUNBERG, Mikael</creatorcontrib><creatorcontrib>GAAL, Emília I</creatorcontrib><creatorcontrib>LAAKSO, Aki</creatorcontrib><creatorcontrib>HERNESNIEMI, Juha</creatorcontrib><creatorcontrib>HUSTON, John</creatorcontrib><creatorcontrib>JÄÄSKELÄINEN, Juha E</creatorcontrib><creatorcontrib>KIEMENEY, Lambertus A</creatorcontrib><creatorcontrib>KIVISAARI, Riku</creatorcontrib><creatorcontrib>KLEINDORFER, Dawn</creatorcontrib><creatorcontrib>KOLLER, Daniel</creatorcontrib><creatorcontrib>KO, Nerissa</creatorcontrib><creatorcontrib>LEHTO, Hanna</creatorcontrib><creatorcontrib>MACKEY, Jason</creatorcontrib><creatorcontrib>MEISSNER, Irene</creatorcontrib><creatorcontrib>MOOMAW, Charles J</creatorcontrib><creatorcontrib>MOSLEY, Thomas H</creatorcontrib><creatorcontrib>MOSKALA, Marek</creatorcontrib><creatorcontrib>NIEMELÄ, Mika</creatorcontrib><creatorcontrib>PALOTIE, Aarno</creatorcontrib><creatorcontrib>PERA, Joanna</creatorcontrib><creatorcontrib>VAN'T HOF, Femke</creatorcontrib><creatorcontrib>RINKEL, Gabriel</creatorcontrib><creatorcontrib>RIPKE, Stephan</creatorcontrib><creatorcontrib>ROULEAU, Guy</creatorcontrib><creatorcontrib>RUIGROK, Ynte</creatorcontrib><creatorcontrib>SAUERBECK, Laura</creatorcontrib><creatorcontrib>SLOWIK, Agnieszka</creatorcontrib><creatorcontrib>VERMEULEN, Sita H</creatorcontrib><creatorcontrib>WOO, Daniel</creatorcontrib><creatorcontrib>WORRALL, Bradford B</creatorcontrib><creatorcontrib>BRODERICK, Joseph</creatorcontrib><creatorcontrib>KURKI, Mitja I</creatorcontrib><creatorcontrib>ANDERSON, Craig S</creatorcontrib><creatorcontrib>BROWN, Robert D</creatorcontrib><creatorcontrib>CONNOLLY, Edward Sander</creatorcontrib><creatorcontrib>ERIKSSON, Johan G</creatorcontrib><creatorcontrib>FLAHERTY, Matthew</creatorcontrib><creatorcontrib>Familial Intracranial Aneurysm Study Investigators</creatorcontrib><title>Genome-Wide Association Study of Intracranial Aneurysm Identifies a New Association on Chromosome 7</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>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.
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.
Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-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=9.91×10(-10)).
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.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Chromosomes, Human, Pair 7 - genetics</subject><subject>Cohort Studies</subject><subject>Diseases of the nervous system</subject><subject>Female</subject><subject>Genome-Wide Association Study - methods</subject><subject>Humans</subject><subject>Intracranial Aneurysm - diagnosis</subject><subject>Intracranial Aneurysm - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>White People - genetics</subject><issn>0039-2499</issn><issn>1524-4628</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUcFq3DAUFKGl2aT9g1B0KfTiVJIlWboUzJImS0IDTUqPQpafs2ptK5Hslv37aNlN0oBADG9m3mMGoRNKTimV9EuaYvgDdm0z5KeESKLlAVpQwXjBJVNv0IKQUheMa32IjlL6TQhhpRLv0CETTEiq2AK5cxjDAMUv3wKuUwrO28mHEd9Mc7vBocOrcYrWRTt62-N6hDlu0oBXLYyT7zwkbPF3-PdKm99yHcMQUrbG1Xv0trN9gg_7_xj9_HZ2u7worq7PV8v6qnCC8KlQwnLR0M5VFVRUd60qgavGZeBUQ5s8rgQQyrnSxDGmKwlaM9lwK1qQtDxGX3e-93MzQOtge3lv7qMfbNyYYL15PRn92tyFv4YzWjK1Nfi8N4jhYYY0mcEnB31vRwhzMjl2RXkOlWcq31FdDClF6J7XUGK2_Zib2x_Xl2f1RZ0hN7t-suzj_yc-i54KyYRPe4JNzvZdzt359MJTWlIiq_IRCbibuQ</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>FOROUD, Tatiana</creator><creator>DONGBING LAI</creator><creator>FORNAGE, Myriam</creator><creator>VON UND ZU FRAUNBERG, Mikael</creator><creator>GAAL, Emília I</creator><creator>LAAKSO, Aki</creator><creator>HERNESNIEMI, Juha</creator><creator>HUSTON, John</creator><creator>JÄÄSKELÄINEN, Juha E</creator><creator>KIEMENEY, Lambertus A</creator><creator>KIVISAARI, Riku</creator><creator>KLEINDORFER, Dawn</creator><creator>KOLLER, Daniel</creator><creator>KO, Nerissa</creator><creator>LEHTO, Hanna</creator><creator>MACKEY, Jason</creator><creator>MEISSNER, Irene</creator><creator>MOOMAW, Charles J</creator><creator>MOSLEY, Thomas H</creator><creator>MOSKALA, Marek</creator><creator>NIEMELÄ, Mika</creator><creator>PALOTIE, Aarno</creator><creator>PERA, Joanna</creator><creator>VAN'T HOF, Femke</creator><creator>RINKEL, Gabriel</creator><creator>RIPKE, Stephan</creator><creator>ROULEAU, Guy</creator><creator>RUIGROK, Ynte</creator><creator>SAUERBECK, Laura</creator><creator>SLOWIK, Agnieszka</creator><creator>VERMEULEN, Sita H</creator><creator>WOO, Daniel</creator><creator>WORRALL, Bradford B</creator><creator>BRODERICK, Joseph</creator><creator>KURKI, Mitja I</creator><creator>ANDERSON, Craig S</creator><creator>BROWN, Robert D</creator><creator>CONNOLLY, Edward Sander</creator><creator>ERIKSSON, Johan G</creator><creator>FLAHERTY, Matthew</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20141101</creationdate><title>Genome-Wide Association Study of Intracranial Aneurysm Identifies a New Association on Chromosome 7</title><author>FOROUD, Tatiana ; DONGBING LAI ; FORNAGE, Myriam ; VON UND ZU FRAUNBERG, Mikael ; GAAL, Emília I ; LAAKSO, Aki ; HERNESNIEMI, Juha ; HUSTON, John ; JÄÄSKELÄINEN, Juha E ; KIEMENEY, Lambertus A ; KIVISAARI, Riku ; KLEINDORFER, Dawn ; KOLLER, Daniel ; KO, Nerissa ; LEHTO, Hanna ; MACKEY, Jason ; MEISSNER, Irene ; MOOMAW, Charles J ; MOSLEY, Thomas H ; MOSKALA, Marek ; NIEMELÄ, Mika ; PALOTIE, Aarno ; PERA, Joanna ; VAN'T HOF, Femke ; RINKEL, Gabriel ; RIPKE, Stephan ; ROULEAU, Guy ; RUIGROK, Ynte ; SAUERBECK, Laura ; SLOWIK, Agnieszka ; VERMEULEN, Sita H ; WOO, Daniel ; WORRALL, Bradford B ; BRODERICK, Joseph ; KURKI, Mitja I ; ANDERSON, Craig S ; BROWN, Robert D ; CONNOLLY, Edward Sander ; ERIKSSON, Johan G ; FLAHERTY, Matthew</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-85a45b1fc77e719fd83e48bce71c8b1b5a475e0144890c22976e9926b4a5de613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Chromosomes, Human, Pair 7 - genetics</topic><topic>Cohort Studies</topic><topic>Diseases of the nervous system</topic><topic>Female</topic><topic>Genome-Wide Association Study - methods</topic><topic>Humans</topic><topic>Intracranial Aneurysm - diagnosis</topic><topic>Intracranial Aneurysm - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Radiotherapy. 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However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk.
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.
Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-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=9.91×10(-10)).
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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>25256182</pmid><doi>10.1161/strokeaha.114.006096</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4213281 |
| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Adult Aged Biological and medical sciences Chromosomes, Human, Pair 7 - genetics Cohort Studies Diseases of the nervous system Female Genome-Wide Association Study - methods Humans Intracranial Aneurysm - diagnosis Intracranial Aneurysm - genetics Male Medical sciences Middle Aged Neurology Polymorphism, Single Nucleotide - genetics Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Vascular diseases and vascular malformations of the nervous system White People - genetics |
| title | Genome-Wide Association Study of Intracranial Aneurysm Identifies a New Association on Chromosome 7 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T16%3A30%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-Wide%20Association%20Study%20of%20Intracranial%20Aneurysm%20Identifies%20a%20New%20Association%20on%20Chromosome%207&rft.jtitle=Stroke%20(1970)&rft.au=FOROUD,%20Tatiana&rft.aucorp=Familial%20Intracranial%20Aneurysm%20Study%20Investigators&rft.date=2014-11-01&rft.volume=45&rft.issue=11&rft.spage=3194&rft.epage=3199&rft.pages=3194-3199&rft.issn=0039-2499&rft.eissn=1524-4628&rft.coden=SJCCA7&rft_id=info:doi/10.1161/strokeaha.114.006096&rft_dat=%3Cproquest_pubme%3E1618140394%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1618140394&rft_id=info:pmid/25256182&rfr_iscdi=true |