GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

N Franceschini; C Giambartolomei; PS de Vries; C Finan; JC Bis; RP Huntley; RC Lovering; SM Tajuddin; TW Winkler; M Graff; M Kavousi; C Dale; AV Smith; E Hofer; EM van Leeuwen; IM Nolte; L Lu; M Scholz; M Sargurupremraj; N Pitkänen; O Franzén; PK Joshi; R Noordam; RE Marioni; SJ Hwang; SK Musani; U Schminke; W Palmas; A Isaacs; A Correa; AB Zonderman; A Hofman; A Teumer; AJ Cox; AG Uitterlinden; A Wong; AJ Smit; AB Newman; A Britton; A Ruusalepp; B Sennblad; B Hedblad; B Pasaniuc; BW Penninx; CD Langefeld; CL Wassel; C Tzourio; C Fava; D Baldassarre; DH O’Leary; D Teupser; D Kuh; E Tremoli; E Mannarino; E Grossi; E Boerwinkle; EE Schadt; E Ingelsson; F Veglia; F Rivadeneira; F Beutner; G Chauhan; G Heiss; H Snieder; H Campbell; H Völzke; HS Markus; IJ Deary; JW Jukema; J de Graaf; J Price; J Pott; JC Hopewell; J Liang; J Thiery; J Engmann; K Gertow; K Rice; KD Taylor; K Dhana; LALM Kiemeney; L Lind; LM Raffield; LJ Launer; LM Holdt; M Dörr; M Dichgans; M Traylor; M Sitzer; M Kumari; M Kivimaki; MA Nalls; O Melander; O Raitakari; OH Franco; OL Rueda-Ochoa; P Roussos; PH Whincup; P Amouyel; P Giral

Journal article

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

N Franceschini, C Giambartolomei, PS de Vries, C Finan, JC Bis, RP Huntley, RC Lovering, SM Tajuddin, TW Winkler, M Graff, M Kavousi, C Dale, AV Smith, E Hofer, EM van Leeuwen, IM Nolte, L Lu, M Scholz, M Sargurupremraj, N Pitkänen Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2018

DOI: 10.1038/s41467-018-07340-5

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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 pote..

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University of Melbourne Researchers

Vincent Thijs Author

Grants

Awarded by Bundesministerium für Bildung und Forschung

Funding Acknowledgements

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.