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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- Source :
- Nature Communications, 9:5141. Nature Publishing Group, Nature Communications, 9, Franceschini, N, Giambartolomei, C, De Vries, P S, Finan, C, Bis, J C, Huntley, R P, Lovering, R C, Tajuddin, S M, Winkler, T W, Graff, M, Kavousi, M, Dale, C, Smith, A V, Hofer, E, Van Leeuwen, E M, Nolte, I M, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, P K, Noordam, R, Marioni, R E, Hwang, S, Musani, S K, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, A B, Hofman, A, Teumer, A, Cox, A J, Uitterlinden, A G, Wong, A, Smit, A J, Newman, A B, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, B W, Langefeld, C D, Wassel, C L, Tzourio, C, Fava, C, Baldassarre, D, O’leary, D H, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, E E, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, H S, Deary, I J, Jukema, J W, De Graaf, J, Price, J, Pott, J, Hopewell, J C, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, K D, Dhana, K, Kiemeney, L A L M, Lind, L, Raffield, L M, Launer, L J, Holdt, L M, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, M A, Melander, O, Raitakari, O, Franco, O H, Rueda-ochoa, O L, Roussos, P, Whincup, P H, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, De Mutsert, R, Morris, R W, Strawbridge, R J, Wannamethee, S G, Hägg, S, Shah, S, Mclachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, S R, Ring, S, Harris, T B, Lehtimäki, T, Galesloot, T E, Shah, T, De Faire, U, Plagnol, V, Rosamond, W D, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, A C, Hamsten, A, Psaty, B M, Van Duijn, C M, Lawlor, D A, Mook-kanamori, D O, Bowden, D W, Schmidt, H, Wilson, J G, Rotter, J I, Wardlaw, J M, Deanfield, J, Halcox, J, Lyytikäinen, L, Loeffler, M, Evans, M K, Debette, S, Humphries, S E, Völker, U, Gudnason, V, Hingorani, A D, Björkegren, J L M, Casas, J P & O’donnell, C J 2018, ' GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes ', Nature Communications, vol. 9, no. 1, 5141 . https://doi.org/10.1038/s41467-018-07340-5, Franceschini, Nora; Giambartolomei, Claudia; de Vries, Paul S; Finan, Chris; Bis, Joshua C; Huntley, Rachael P; Lovering, Ruth C; Tajuddin, Salman M; Winkler, Thomas W; Graff, Misa; Kavousi, Maryam; Dale, Caroline; Smith, Albert V; Hofer, Edith; van Leeuwen, Elisabeth M; Nolte, Ilja M; Lu, Lingyi; Scholz, Markus; Sargurupremraj, Muralidharan; Pitkänen, Niina; ... (2018). GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nature communications, 9(1), p. 5141. Nature Publishing Group 10.1038/s41467-018-07340-5
- Publication Year :
- 2018
-
Abstract
- Publisher's version (útgefin grein)<br />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.<br />The work was supported by the following grants: National Institute of Health grants: R21HL123677, R21-HL140385, DK104806-01A1, R01-MD012765-01A1 (NF), National Institutes of Health awards R01HG009120, R01HG006399, U01CA194393, T32NS048004 (CG), the American Heart Association Grant #17POST33350042 (PV), the British Heart Foundation (RG/13/5/30112) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (RCL and RPH), the British Heart Foundation FS/14/55/30806 (JCH), the German Federal Ministry of Education and Research (BMBF) in the context of the e:Med program (e:AtheroSysMed), the DFG as part of the CRC 1123 (B3), and the FP7/2007-2103 European Union project CVgenes@target (grant agreement number Health-F2-2013-601456). We thank Li-Ming Gan for assistance with the STARNET study and Jon White for assistance with UCLEB analyses. Additional acknowledgements are included in Supplementary Note 2.
- Subjects :
- 0301 basic medicine
Candidate gene
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
General Physics and Astronomy
Genome-wide association study
Coronary Disease
VARIANTS
Carotid Intima-Media Thickness
Coronary artery disease
Protein-Lysine 6-Oxidase
Risk Factors
Medicine
genetics
Cardiac and Cardiovascular Systems
Blóðrásarsjúkdómar
lcsh:Science
GENE-PRODUCT
cardiovascular genetics
Multidisciplinary
Kardiologi
Plaque, Atherosclerotic
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
Cardiology
cardiovascular system
Medical genetics
CORONARY-ARTERY-DISEASE
HEART
Amino Acid Oxidoreductases
Erfðarannsóknir
Medical Genetics
medicine.medical_specialty
MEGASTROKE Consortium
Science
Quantitative Trait Loci
ADAMTS9 Protein
INTEGRATIVE ANALYSIS
Locus (genetics)
610 Medicine & health
Quantitative trait locus
Polymorphism, Single Nucleotide
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
360 Social problems & social services
Internal medicine
MD Multidisciplinary
Humans
Erfðafræði
intima media thickness
Genetic Predisposition to Disease
cardiovascular diseases
GENOME-WIDE ASSOCIATION
METAANALYSIS
Genetic association
Medicinsk genetik
business.industry
General Chemistry
medicine.disease
030104 developmental biology
Intima-media thickness
genome-wide association studies
quantitative trait loci
lcsh:Q
atherosclerosis
Lod Score
hjarta
business
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 9:5141. Nature Publishing Group, Nature Communications, 9, Franceschini, N, Giambartolomei, C, De Vries, P S, Finan, C, Bis, J C, Huntley, R P, Lovering, R C, Tajuddin, S M, Winkler, T W, Graff, M, Kavousi, M, Dale, C, Smith, A V, Hofer, E, Van Leeuwen, E M, Nolte, I M, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, P K, Noordam, R, Marioni, R E, Hwang, S, Musani, S K, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, A B, Hofman, A, Teumer, A, Cox, A J, Uitterlinden, A G, Wong, A, Smit, A J, Newman, A B, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, B W, Langefeld, C D, Wassel, C L, Tzourio, C, Fava, C, Baldassarre, D, O’leary, D H, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, E E, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, H S, Deary, I J, Jukema, J W, De Graaf, J, Price, J, Pott, J, Hopewell, J C, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, K D, Dhana, K, Kiemeney, L A L M, Lind, L, Raffield, L M, Launer, L J, Holdt, L M, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, M A, Melander, O, Raitakari, O, Franco, O H, Rueda-ochoa, O L, Roussos, P, Whincup, P H, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, De Mutsert, R, Morris, R W, Strawbridge, R J, Wannamethee, S G, Hägg, S, Shah, S, Mclachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, S R, Ring, S, Harris, T B, Lehtimäki, T, Galesloot, T E, Shah, T, De Faire, U, Plagnol, V, Rosamond, W D, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, A C, Hamsten, A, Psaty, B M, Van Duijn, C M, Lawlor, D A, Mook-kanamori, D O, Bowden, D W, Schmidt, H, Wilson, J G, Rotter, J I, Wardlaw, J M, Deanfield, J, Halcox, J, Lyytikäinen, L, Loeffler, M, Evans, M K, Debette, S, Humphries, S E, Völker, U, Gudnason, V, Hingorani, A D, Björkegren, J L M, Casas, J P & O’donnell, C J 2018, ' GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes ', Nature Communications, vol. 9, no. 1, 5141 . https://doi.org/10.1038/s41467-018-07340-5, Franceschini, Nora; Giambartolomei, Claudia; de Vries, Paul S; Finan, Chris; Bis, Joshua C; Huntley, Rachael P; Lovering, Ruth C; Tajuddin, Salman M; Winkler, Thomas W; Graff, Misa; Kavousi, Maryam; Dale, Caroline; Smith, Albert V; Hofer, Edith; van Leeuwen, Elisabeth M; Nolte, Ilja M; Lu, Lingyi; Scholz, Markus; Sargurupremraj, Muralidharan; Pitkänen, Niina; ... (2018). GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nature communications, 9(1), p. 5141. Nature Publishing Group 10.1038/s41467-018-07340-5 <http://dx.doi.org/10.1038/s41467-018-07340-5>, Giambartolomei, C, de Vries, P S, Finan, C, Bis, J C, Huntley, R P, Lovering, R C, Tajuddin, S M, Winkler, T W, Graff, M, Kavousi, M, Dale, C, Smith, A V, Hofer, E, van Leeuwen, E M, Nolte, I M, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, P K, Noordam, R, Marioni, R E, Hwang, S-J, Musani, S K, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, A B, Hofman, A, Teumer, A, Cox, A J, Uitterlinden, A G, Wong, A, Smit, A J, Newman, A B, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Kuh, D, Kumari, M, Kivimaki, M, Morris, R W, Ring, S & Wilson, J G & Deanfield, J 2018, ' GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes ', Nature Communications, vol. 9, 5141 . https://doi.org/10.1038/s41467-018-07340-5, Franceschini, N, Giambartolomei, C, de Vries, P S, Finan, C, Bis, J C, Huntley, R P, Lovering, R C, Tajuddin, S M, Winkler, T W, Graff, M, Kavousi, M, Dale, C, Smith, A V, Hofer, E, van Leeuwen, E M, Nolte, I M, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, P K, Noordam, R, Marioni, R E, Hwang, S-J, Musani, S K, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, A B, Hofman, A, Teumer, A, Cox, A J, Uitterlinden, A G, Wong, A, Smit, A J, Newman, A B, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, B W, Langefeld, C D, Wassel, C L, Tzourio, C, Adams, H H H, Seldenrijk, A, Adams, H H H & MEGASTROKE Consortium 2018, ' GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes ', Nature Communications, vol. 9, no. 1, 5141 . https://doi.org/10.1038/s41467-018-07340-5, Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018), Nature Communications, 9(1):5141. Nature Publishing Group, Franceschini, N, Giambartolomei, C, De Vries, P S, Finan, C, Bis, J C, Huntley, R P, Lovering, R C, Tajuddin, S M, Winkler, T W, Graff, M, Kavousi, M, Dale, C, Smith, A V, Hofer, E, Van Leeuwen, E M, Nolte, I M, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, P K, Noordam, R, Marioni, R E, Hwang, S, Musani, S K, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, A B, Hofman, A, Teumer, A, Cox, A J, Uitterlinden, A G, Wong, A, Smit, A J, Newman, A B, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, B W, Langefeld, C D, Wassel, C L, Tzourio, C, Fava, C, Baldassarre, D, O’leary, D H, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, E E, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, H S, Deary, I J, Jukema, J W, De Graaf, J, Price, J, Pott, J, Hopewell, J C, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, K D, Dhana, K, Kiemeney, L A L M, Lind, L, Raffield, L M, Launer, L J, Holdt, L M, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, M A, Melander, O, Raitakari, O, Franco, O H, Rueda-ochoa, O L, Roussos, P, Whincup, P H, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, De Mutsert, R, Morris, R W, Strawbridge, R J, Wannamethee, S G, Hägg, S, Shah, S, Mclachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, S R, Ring, S, Harris, T B, Lehtimäki, T, Galesloot, T E, Shah, T, De Faire, U, Plagnol, V, Rosamond, W D, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, A C, Hamsten, A, Psaty, B M, Van Duijn, C M, Lawlor, D A, Mook-kanamori, D O, Bowden, D W, Schmidt, H, Wilson, J G, Wilson, J G, Rotter, J I, Wardlaw, J M, Deanfield, J, Halcox, J, Lyytikäinen, L, Loeffler, M, Evans, M K, Debette, S, Humphries, S E, Völker, U, Gudnason, V, Hingorani, A D, Björkegren, J L M, Casas, J P & O’donnell, C J 2018, ' GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes ' vol. 9, no. 1, 5141 . DOI: 10.1038/s41467-018-07340-5, Nature Communications, Nature communications, 9(1):5141. Nature Publishing Group
- Accession number :
- edsair.doi.dedup.....c1e74c44615367f516a16ae2ad5edfaa