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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
| File | Description | Size | Format | |
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 GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.pdf | Published version | 1.67 MB | Adobe PDF | View/Open |
| Title: | GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes |
| Authors: | Franceschini, N Giambartolomei, C De Vries, PS Finan, C Bis, JC Huntley, RP Lovering, RC Tajuddin, SM Winkler, TW Graff, M Kavousi, M Dale, C Smith, AV Hofer, E Van Leeuwen, EM Nolte, IM Lu, L Scholz, M Sargurupremraj, M Pitkänen, N Franzén, O Joshi, PK Noordam, R Marioni, RE Hwang, S-J Musani, SK Schminke, U Palmas, W Isaacs, A Correa, A Zonderman, AB Hofman, A Teumer, A Cox, AJ Uitterlinden, AG Wong, A Smit, AJ Newman, AB Britton, A Ruusalepp, A Sennblad, B Hedblad, B Pasaniuc, B Penninx, BW Langefeld, CD Wassel, CL Tzourio, C Fava, C Baldassarre, D O'Leary, DH Teupser, D Kuh, D Tremoli, E Mannarino, E Grossi, E Boerwinkle, E Schadt, EE Ingelsson, E Veglia, F Rivadeneira, F Beutner, F Chauhan, G Heiss, G Snieder, H Campbell, H Völzke, H Markus, HS Deary, IJ Jukema, JW De Graaf, J Price, J Pott, J Hopewell, JC Liang, J Thiery, J Engmann, J Gertow, K Rice, K Taylor, KD Dhana, K Kiemeney, LALM Lind, L Raffield, LM Launer, LJ Holdt, LM Dörr, M Dichgans, M Traylor, M Sitzer, M Kumari, M Kivimaki, M Nalls, MA Melander, O Raitakari, O Franco, OH Rueda-Ochoa, OL Roussos, P Whincup, PH Amouyel, P Giral, P Anugu, P Wong, Q Malik, R Rauramaa, R Burkhardt, R Hardy, R Schmidt, R De Mutsert, R Morris, RW Strawbridge, RJ Wannamethee, SG Hägg, S Shah, S McLachlan, S Trompet, S Seshadri, S Kurl, S Heckbert, SR Ring, S Harris, TB Lehtimäki, T Galesloot, TE Shah, T De Faire, U Plagnol, V Rosamond, WD Post, W Zhu, X Zhang, X Guo, X Saba, Y MEGASTROKE Consortium Dehghan, A Seldenrijk, A Morrison, AC Hamsten, A Psaty, BM Van Duijn, CM Lawlor, DA Mook-Kanamori, DO Bowden, DW Schmidt, H Wilson, JF Wilson, JG Rotter, JI Wardlaw, JM Deanfield, J Halcox, J Lyytikäinen, L-P Loeffler, M Evans, MK Debette, S Humphries, SE Völker, U Gudnason, V Hingorani, AD Björkegren, JLM Casas, JP O'Donnell, CJ |
| Item Type: | Journal Article |
| Abstract: | Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. |
| Issue Date: | 3-Dec-2018 |
| Date of Acceptance: | 24-Sep-2018 |
| URI: | http://hdl.handle.net/10044/1/67378 |
| DOI: | https://dx.doi.org/10.1038/s41467-018-07340-5 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Research (part of Springer Nature) |
| Journal / Book Title: | Nature Communications |
| Volume: | 9 |
| Issue: | 1 |
| Copyright Statement: | © 2018 The Author(s). This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/ |
| Keywords: | ADAMTS9 Protein Amino Acid Oxidoreductases Carotid Intima-Media Thickness Coronary Disease Genetic Predisposition to Disease Genome-Wide Association Study Humans Lod Score Plaque, Atherosclerotic Polymorphism, Single Nucleotide Quantitative Trait Loci Risk Factors MEGASTROKE Consortium MD Multidisciplinary |
| Publication Status: | Published |
| Conference Place: | England |
| Article Number: | ARTN 5141 |
| Appears in Collections: | School of Public Health |