Search: onr:"swepub:oai:lup.lub.lu.se:f1c94f96-f94f-452d-9a4f-565689a974c1" > A Novel MMP12 Locus...
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000 | 05080naa a2200781 4500 | |
001 | oai:lup.lub.lu.se:f1c94f96-f94f-452d-9a4f-565689a974c1 | |
003 | SwePub | |
008 | 160401s2014 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/46159472 URI |
024 | 7 | a https://doi.org/10.1371/journal.pgen.10044692 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Traylor, Matthew4 aut |
245 | 1 0 | a A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach. |
264 | c 2014-07-31 | |
264 | 1 | b Public Library of Science (PLoS),c 2014 |
338 | a electronic2 rdacarrier | |
520 | a Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10-7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05-1.32); meta-analysis p = 2.6×10-8). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10-15; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
700 | 1 | a Mäkelä, Kari-Matti4 aut |
700 | 1 | a Kilarski, Laura L4 aut |
700 | 1 | a Holliday, Elizabeth G4 aut |
700 | 1 | a Devan, William J4 aut |
700 | 1 | a Nalls, Mike A4 aut |
700 | 1 | a Wiggins, Kerri L4 aut |
700 | 1 | a Zhao, Wei4 aut |
700 | 1 | a Cheng, Yu-Ching4 aut |
700 | 1 | a Achterberg, Sefanja4 aut |
700 | 1 | a Malik, Rainer4 aut |
700 | 1 | a Sudlow, Cathie4 aut |
700 | 1 | a Bevan, Steve4 aut |
700 | 1 | a Raitoharju, Emma4 aut |
700 | 1 | a Oksala, Niku4 aut |
700 | 1 | a Thijs, Vincent4 aut |
700 | 1 | a Lemmens, Robin4 aut |
700 | 1 | a Lindgren, Arneu Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)neur-ali |
700 | 1 | a Slowik, Agnieszka4 aut |
700 | 1 | a Maguire, Jane M4 aut |
700 | 1 | a Walters, Matthew4 aut |
700 | 1 | a Algra, Ale4 aut |
700 | 1 | a Sharma, Pankaj4 aut |
700 | 1 | a Attia, John R4 aut |
700 | 1 | a Boncoraglio, Giorgio B4 aut |
700 | 1 | a Rothwell, Peter M4 aut |
700 | 1 | a de Bakker, Paul I W4 aut |
700 | 1 | a Bis, Joshua C4 aut |
700 | 1 | a Saleheen, Danish4 aut |
700 | 1 | a Kittner, Steven J4 aut |
700 | 1 | a Mitchell, Braxton D4 aut |
700 | 1 | a Rosand, Jonathan4 aut |
700 | 1 | a Meschia, James F4 aut |
700 | 1 | a Levi, Christopher4 aut |
700 | 1 | a Dichgans, Martin4 aut |
700 | 1 | a Lehtimäki, Terho4 aut |
700 | 1 | a Lewis, Cathryn M4 aut |
700 | 1 | a Markus, Hugh S4 aut |
710 | 2 | a Neurologi, Lundb Sektion IV4 org |
773 | 0 | t PLoS Geneticsd : Public Library of Science (PLoS)g 10:7q 10:7x 1553-7404 |
856 | 4 | u https://portal.research.lu.se/files/2449499/8146603.pdfx primaryx freey FULLTEXT |
856 | 4 | u http://www.ncbi.nlm.nih.gov/pubmed/25078452?dopt=Abstractx freey FULLTEXT |
856 | 4 | u http://dx.doi.org/10.1371/journal.pgen.1004469x freey FULLTEXT |
856 | 4 | u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004469&type=printable |
856 | 4 8 | u https://lup.lub.lu.se/record/4615947 |
856 | 4 8 | u https://doi.org/10.1371/journal.pgen.1004469 |
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