Genetic Variation at 16q24.2 is associated with small vessel stroke.

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Traylor, MatthewKing's College London (author)

Genetic Variation at 16q24.2 is associated with small vessel stroke.

Article/chapterEnglish2017

Publisher, publication year, extent ...

2017-03-25
Wiley,2017

Numbers

LIBRIS-ID:oai:gup.ub.gu.se/247899
https://gup.ub.gu.se/publication/247899URI
https://doi.org/10.1002/ana.24840DOI
https://lup.lub.lu.se/record/ad82f8ae-3860-453e-9326-5c2cd7d74ba4URI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises a quarter of all ischaemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown younger onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger onset SVS population, to identify novel associations with stroke.We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on mRNA expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain.We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (OR(95% CI)=1.16(1.10-1.22); p=3.2x10(-9) ). The lead SNP (rs12445022) was also associated with cerebral white matter hyperintensities (OR(95% CI)=1.10(1.05-1.16); p=5.3x10(-5) ; N=3,670), but not intracerebral haemorrhage (OR(95% CI)=0.97(0.84-1.12); p=0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p=9.4x10(-7) ), and DNA methylation at probe cg16596957 in whole blood (p=5.3x10(-6) ).16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. This article is protected by copyright. All rights reserved.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
genetic variation
small vessel stroke
16q24.2

Added entries (persons, corporate bodies, meetings, titles ...)

Malik, RainerUniversity Hospital Munich (author)
Nalls, Mike ANational Institute on Aging, United States (author)
Cotlarciuc, IoanaRoyal Holloway University of London (author)
Radmanesh, FaridMassachusetts General Hospital (author)
Thorleifsson, GudmardeCODE Genetics (author)
Hanscombe, Ken BKing's College London (author)
Langefeld, CarlWake Forest University (author)
Saleheen, DanishUniversity of Pennsylvania (author)
Rost, Natalia SMassachusetts General Hospital,Framingham Heart Study,Boston University (author)
Yet, IdilKing's College London (author)
Spector, Tim DKing's College London (author)
Bell, Jordana TKing's College London (author)
Hannon, EilisUniversity of Exeter (author)
Mill, JonathanKing's College London,University of Exeter (author)
Chauhan, GaneshInstitut Gustave Roussy,University of Bordeaux (author)
Debette, StephanieUniversity of Bordeaux,Institut Gustave Roussy (author)
Bis, Joshua CUniversity of Washington (author)
Longstreth, W TUniversity of Washington (author)
Ikram, M ArfanErasmus University Medical Center (author)
Launer, Lenore JNational Institute on Aging, United States (author)
Seshadri, Sudha (author)
Jimenez-Conde, JordiHospital del Mar Medical Research Institute (author)
Cole, John WSlotervaart Hospital (author)
Schmidt, ReinholdMedical University of Graz (author)
Słowik, AgnieszkaJagiellonian University (author)
Lemmens, RobinUniversity Hospitals Leuven,Catholic University of Leuven (author)
Lindgren, ArneLund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)neur-ali (author)
Melander, OlleLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine(Swepub:lu)endo-ome (author)
Grewal, Raji PSeton Hall University (author)
Sacco, Ralph LUniversity of Miami (author)
Rundek, TatjanaUniversity of Miami (author)
Rexrode, KathrynBrigham and Women's Hospital / Harvard Medical School (author)
Arnett, Donna KUniversity of Kentucky (author)
Johnson, Julie AFlorida Museum Natural History (author)
Benavente, Oscar RUniversity of British Columbia (author)
Wasssertheil-Smoller, SylviaYeshiva University (author)
Lee, Jin-MooWashington University School of Medicine (author)
Pulit, Sara LUniversity Medical Center Utrecht (author)
Wong, QuennaUniversity of Washington (author)
Rich, Stephen SUniversity of Virginia School of Medicine (author)
de Bakker, Paul I WUniversity Medical Center Utrecht (author)
McArdle, Patrick FSlotervaart Hospital (author)
Woo, DanielUniversity of Cincinnati College of Medicine (author)
Anderson, Christopher DMassachusetts General Hospital,Broad Institute (author)
Xu, HuichunSlotervaart Hospital (author)
Heitsch, LauraWashington University in St. Louis (author)
Fornage, MyriamUniversity of Texas (author)
Jern, Christina,1962Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Sahlgrenska Academy(Swepub:gu)xjerch (author)
Stefansson, Kari (author)
Thorsteinsdottir, Unnur (author)
Gretarsdottir, Solveig (author)
Lewis, Cathryn M (author)
Sharma, Pankaj (author)
Sudlow, Cathie L M (author)
Rothwell, Peter M (author)
Boncoraglio, Giorgio B (author)
Thijs, Vincent (author)
Levi, Chris (author)
Meschia, James F (author)
Rosand, Jonathan (author)
Kittner, Steven J (author)
Mitchell, Braxton D (author)
Dichgans, Martin (author)
Worrall, Bradford B (author)
Markus, Hugh S (author)
Hamilton-Bruce, Monica AnneRoyal Adelaide Hospital (author)
King's College LondonUniversity Hospital Munich (creator_code:org_t)
on behalf of the International Stroke Genetics Consortium

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In:Annals of neurology: Wiley81:3, s. 383-3941531-82490364-5134

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By the author/editor: Traylor, Matthew; Malik, Rainer; Nalls, Mike A; Cotlarciuc, Ioan ...; Radmanesh, Farid; Thorleifsson, Gu ...; show more...; Hanscombe, Ken B; Langefeld, Carl; Saleheen, Danish; Rost, Natalia S; Yet, Idil; Spector, Tim D; Bell, Jordana T; Hannon, Eilis; Mill, Jonathan; Chauhan, Ganesh; Debette, Stephan ...; Bis, Joshua C; Longstreth, W T; Ikram, M Arfan; Launer, Lenore J; Seshadri, Sudha; Jimenez-Conde, J ...; Cole, John W; Schmidt, Reinhol ...; Słowik, Agnieszk ...; Lemmens, Robin; Lindgren, Arne; Melander, Olle; Grewal, Raji P; Sacco, Ralph L; Rundek, Tatjana; Rexrode, Kathryn; Arnett, Donna K; Johnson, Julie A; Benavente, Oscar ...; Wasssertheil-Smo ...; Lee, Jin-Moo; Pulit, Sara L; Wong, Quenna; Rich, Stephen S; de Bakker, Paul ...; McArdle, Patrick ...; Woo, Daniel; Anderson, Christ ...; Xu, Huichun; Heitsch, Laura; Fornage, Myriam; Jern, Christina, ...; Stefansson, Kari; Thorsteinsdottir ...; Gretarsdottir, S ...; Lewis, Cathryn M; Sharma, Pankaj; Sudlow, Cathie L ...; Rothwell, Peter ...; Boncoraglio, Gio ...; Thijs, Vincent; Levi, Chris; Meschia, James F; Rosand, Jonathan; Kittner, Steven ...; Mitchell, Braxto ...; Dichgans, Martin; Worrall, Bradfor ...; Markus, Hugh S; Hamilton-Bruce, ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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By the university: University of Gothenburg; Lund University

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