No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study
Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these r...
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| description | Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information.
We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke.
We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events. |
| doi_str_mv | 10.1371/journal.pone.0119203 |
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We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke.
We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119203</identifier><identifier>PMID: 25906364</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Analysis ; Area Under Curve ; Arteries - pathology ; Blood platelets ; Brain Ischemia - genetics ; Cardiac arrhythmia ; Cerebral Infarction - genetics ; Cerebral ischemia ; Confidence intervals ; Consortia ; Disease ; Epidemiology ; Female ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study - methods ; Genomes ; Genomics ; Genotype ; Health sciences ; Humans ; Incidence ; Ischemia ; Laboratories ; Male ; Mathematical models ; Middle Aged ; Neurology ; Neurosurgery ; Patients ; Performance enhancement ; Polymorphism, Single Nucleotide - genetics ; Prediction models ; Primary care ; Prognosis ; Risk analysis ; Risk Factors ; ROC Curve ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Stroke ; Stroke - genetics ; Studies ; Vascular Diseases - genetics</subject><ispartof>PloS one, 2015-04, Vol.10 (4), p.e0119203</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Achterberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Achterberg et al 2015 Achterberg et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f2ae75f06a248c2b2f1d60e7fd05f8aa59e0e8b9852740a985cfa24149b67b5e3</citedby><cites>FETCH-LOGICAL-c692t-f2ae75f06a248c2b2f1d60e7fd05f8aa59e0e8b9852740a985cfa24149b67b5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408031/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408031/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25906364$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Minnerup, Jens</contributor><creatorcontrib>Achterberg, Sefanja</creatorcontrib><creatorcontrib>Kappelle, L Jaap</creatorcontrib><creatorcontrib>de Bakker, Paul I W</creatorcontrib><creatorcontrib>Traylor, Matthew</creatorcontrib><creatorcontrib>Algra, Ale</creatorcontrib><creatorcontrib>SMART Study Group and the METASTROKE Consortium</creatorcontrib><creatorcontrib>SMART Study Group and the METASTROKE Consortium</creatorcontrib><title>No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information.
We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke.
We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events.</description><subject>Aged</subject><subject>Analysis</subject><subject>Area Under Curve</subject><subject>Arteries - pathology</subject><subject>Blood platelets</subject><subject>Brain Ischemia - genetics</subject><subject>Cardiac arrhythmia</subject><subject>Cerebral Infarction - genetics</subject><subject>Cerebral ischemia</subject><subject>Confidence intervals</subject><subject>Consortia</subject><subject>Disease</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype</subject><subject>Health sciences</subject><subject>Humans</subject><subject>Incidence</subject><subject>Ischemia</subject><subject>Laboratories</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neurosurgery</subject><subject>Patients</subject><subject>Performance enhancement</subject><subject>Polymorphism, Single Nucleotide - 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Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information.
We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke.
We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25906364</pmid><doi>10.1371/journal.pone.0119203</doi><oa>free_for_read</oa></addata></record> |
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| source | PubMed Central Free; MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Aged Analysis Area Under Curve Arteries - pathology Blood platelets Brain Ischemia - genetics Cardiac arrhythmia Cerebral Infarction - genetics Cerebral ischemia Confidence intervals Consortia Disease Epidemiology Female Genetics Genome-wide association studies Genome-Wide Association Study - methods Genomes Genomics Genotype Health sciences Humans Incidence Ischemia Laboratories Male Mathematical models Middle Aged Neurology Neurosurgery Patients Performance enhancement Polymorphism, Single Nucleotide - genetics Prediction models Primary care Prognosis Risk analysis Risk Factors ROC Curve Single nucleotide polymorphisms Single-nucleotide polymorphism Stroke Stroke - genetics Studies Vascular Diseases - genetics |
| title | No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T08%3A54%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=No%20Additional%20Prognostic%20Value%20of%20Genetic%20Information%20in%20the%20Prediction%20of%20Vascular%20Events%20after%20Cerebral%20Ischemia%20of%20Arterial%20Origin:%20The%20PROMISe%20Study&rft.jtitle=PloS%20one&rft.au=Achterberg,%20Sefanja&rft.aucorp=SMART%20Study%20Group%20and%20the%20METASTROKE%20Consortium&rft.date=2015-04-23&rft.volume=10&rft.issue=4&rft.spage=e0119203&rft.pages=e0119203-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0119203&rft_dat=%3Cgale_plos_%3EA422547872%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1675172014&rft_id=info:pmid/25906364&rft_galeid=A422547872&rft_doaj_id=oai_doaj_org_article_e87fcbc2d6f44184a6906d7a4868f63d&rfr_iscdi=true |