GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
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 individu...
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| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
Nature Research
2018
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| _version_ | 1826256440641191936 |
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| author | 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 Rothwell, PM |
| author_facet | 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 Rothwell, PM |
| author_sort | Franceschini, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:02:19Z |
| format | Journal article |
| id | oxford-uuid:0035f03f-fd0a-447f-99bd-8f782ce2d6e7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:02:19Z |
| publishDate | 2018 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:0035f03f-fd0a-447f-99bd-8f782ce2d6e72022-03-26T08:28:45ZGWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0035f03f-fd0a-447f-99bd-8f782ce2d6e7EnglishSymplectic Elements at OxfordNature Research2018Franceschini, NGiambartolomei, CDe Vries, PSFinan, CBis, JCHuntley, RPLovering, RCTajuddin, SMWinkler, TWGraff, MKavousi, MDale, CSmith, AVHofer, EVan Leeuwen, EMNolte, IMLu, LScholz, MSargurupremraj, MPitkänen, NFranzén, OJoshi, PKNoordam, RMarioni, REHwang, S-JMusani, SKSchminke, UPalmas, WIsaacs, ACorrea, AZonderman, ABHofman, ATeumer, ACox, AJUitterlinden, AGWong, ASmit, AJNewman, ABBritton, ARuusalepp, ASennblad, BHedblad, BPasaniuc, BPenninx, BWLangefeld, CDWassel, CLTzourio, CFava, CBaldassarre, DO'Leary, DHTeupser, DKuh, DTremoli, EMannarino, EGrossi, EBoerwinkle, ESchadt, EEIngelsson, EVeglia, FRivadeneira, FBeutner, FChauhan, GHeiss, GSnieder, HCampbell, HVölzke, HMarkus, HSDeary, IJJukema, JWDe Graaf, JPrice, JPott, JHopewell, JCLiang, JThiery, JEngmann, JGertow, KRice, KTaylor, KDDhana, KKiemeney, LALMLind, LRaffield, LMLauner, LJHoldt, LMDörr, MDichgans, MTraylor, MSitzer, MKumari, MKivimaki, MNalls, MAMelander, ORaitakari, OFranco, OHRueda-Ochoa, OLRoussos, PWhincup, PHAmouyel, PGiral, PAnugu, PWong, QMalik, RRauramaa, RBurkhardt, RHardy, RSchmidt, RDe Mutsert, RMorris, RWStrawbridge, RJWannamethee, SGHägg, SShah, SMcLachlan, STrompet, SSeshadri, SKurl, SHeckbert, SRRing, SHarris, TBLehtimäki, TGalesloot, TEShah, TDe Faire, UPlagnol, VRosamond, WDPost, WZhu, XZhang, XGuo, XSaba, YMegastroke ConsortiumDehghan, ASeldenrijk, AMorrison, ACHamsten, APsaty, BMVan Duijn, CMLawlor, DAMook-Kanamori, DOBowden, DWSchmidt, HWilson, JFWilson, JGRotter, JIWardlaw, JMDeanfield, JHalcox, JLyytikäinen, L-PLoeffler, MEvans, MKDebette, SHumphries, SEVölker, UGudnason, VHingorani, ADBjörkegren, JLMCasas, JPO'Donnell, CJRothwell, PMCarotid 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. |
| spellingShingle | 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 Rothwell, PM GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. |
| title | GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. |
| title_full | GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. |
| title_fullStr | GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. |
| title_full_unstemmed | GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. |
| title_short | GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. |
| title_sort | gwas and colocalization analyses implicate carotid intima media thickness and carotid plaque loci in cardiovascular outcomes |
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