Sökning: WFRF:(Lind L) > Stroke genetics inf...
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000 | 27754naa a2207993 4500 | |
001 | oai:gup.ub.gu.se/322231 | |
003 | SwePub | |
008 | 240910s2022 | |||||||||||000 ||eng| | |
009 | oai:DiVA.org:umu-200734 | |
009 | oai:lup.lub.lu.se:5e54bbd2-c610-458b-81bb-15f6b27f8a9e | |
009 | oai:prod.swepub.kib.ki.se:150831010 | |
024 | 7 | a https://gup.ub.gu.se/publication/3222312 URI |
024 | 7 | a https://doi.org/10.1038/s41586-022-05165-32 DOI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-2007342 URI |
024 | 7 | a https://lup.lub.lu.se/record/5e54bbd2-c610-458b-81bb-15f6b27f8a9e2 URI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1508310102 URI |
040 | a (SwePub)gud (SwePub)umud (SwePub)lud (SwePub)ki | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Mishra, A.u University of Bordeaux4 aut |
245 | 1 0 | a Stroke genetics informs drug discovery and risk prediction across ancestries |
264 | c 2022-09-30 | |
264 | 1 | b Springer Science and Business Media LLC,c 2022 |
500 | a Publisher correction: Mishra, A., Malik, R., Hachiya, T. et al. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 612, E7 (2022). DOI: 10.1038/s41586-022-05492-5 | |
520 | a Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries. | |
650 | 7 | a NATURVETENSKAPx Matematikx Sannolikhetsteori och statistik0 (SwePub)101062 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Mathematicsx Probability Theory and Statistics0 (SwePub)101062 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
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 |
653 | a genome-wide association | |
653 | a mendelian randomization | |
653 | a polygenic risk | |
653 | a heritability | |
653 | a statistics | |
653 | a expression | |
653 | a brain | |
653 | a atlas | |
653 | a regularization | |
653 | a metaanalysis | |
653 | a Science & Technology - Other Topics | |
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773 | 0 | t Natured : Springer Science and Business Media LLCg 611, s. 115-123q 611<115-123x 0028-0836x 1476-4687 |
856 | 4 | u https://doi.org/10.1038/s41586-022-05165-3y Fulltext |
856 | 4 | u https://umu.diva-portal.org/smash/get/diva2:1708228/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 | u http://dx.doi.org/10.1038/s41586-022-05165-3x freey FULLTEXT |
856 | 4 8 | u https://gup.ub.gu.se/publication/322231 |
856 | 4 8 | u https://doi.org/10.1038/s41586-022-05165-3 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200734 |
856 | 4 8 | u https://lup.lub.lu.se/record/5e54bbd2-c610-458b-81bb-15f6b27f8a9e |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:150831010 |
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