Dataset Information

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

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.

SUBMITTER: Franceschini N

PROVIDER: S-EPMC6277418 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Franceschini Nora N Giambartolomei Claudia C de Vries Paul S PS Finan Chris C Bis Joshua C JC Huntley Rachael P RP Lovering Ruth C RC Tajuddin Salman M SM Winkler Thomas W TW Graff Misa M Kavousi Maryam M Dale Caroline C Smith Albert V AV Hofer Edith E van Leeuwen Elisabeth M EM Nolte Ilja M IM Lu Lingyi L Scholz Markus M Sargurupremraj Muralidharan M Pitkänen Niina N Franzén Oscar O Joshi Peter K PK Noordam Raymond R Marioni Riccardo E RE Hwang Shih-Jen SJ Musani Solomon K SK Schminke Ulf U Palmas Walter W Isaacs Aaron A Correa Adolfo A Zonderman Alan B AB Hofman Albert A Teumer Alexander A Cox Amanda J AJ Uitterlinden André G AG Wong Andrew A Smit Andries J AJ Newman Anne B AB Britton Annie A Ruusalepp Arno A Sennblad Bengt B Hedblad Bo B Pasaniuc Bogdan B Penninx Brenda W BW Langefeld Carl D CD Wassel Christina L CL Tzourio Christophe C Fava Cristiano C Baldassarre Damiano D O'Leary Daniel H DH Teupser Daniel D Kuh Diana D Tremoli Elena E Mannarino Elmo E Grossi Enzo E Boerwinkle Eric E Schadt Eric E EE Ingelsson Erik E Veglia Fabrizio F Rivadeneira Fernando F Beutner Frank F Chauhan Ganesh G Heiss Gerardo G Snieder Harold H Campbell Harry H Völzke Henry H Markus Hugh S HS Deary Ian J IJ Jukema J Wouter JW de Graaf Jacqueline J Price Jacqueline J Pott Janne J Hopewell Jemma C JC Liang Jingjing J Thiery Joachim J Engmann Jorgen J Gertow Karl K Rice Kenneth K Taylor Kent D KD Dhana Klodian K Kiemeney Lambertus A L M LALM Lind Lars L Raffield Laura M LM Launer Lenore J LJ Holdt Lesca M LM Dörr Marcus M Dichgans Martin M Traylor Matthew M Sitzer Matthias M Kumari Meena M Kivimaki Mika M Nalls Mike A MA Melander Olle O Raitakari Olli O Franco Oscar H OH Rueda-Ochoa Oscar L OL Roussos Panos P Whincup Peter H PH Amouyel Philippe P Giral Philippe P Anugu Pramod P Wong Quenna Q Malik Rainer R Rauramaa Rainer R Burkhardt Ralph R Hardy Rebecca R Schmidt Reinhold R de Mutsert Renée R Morris Richard W RW Strawbridge Rona J RJ Wannamethee S Goya SG Hägg Sara S Shah Sonia S McLachlan Stela S Trompet Stella S Seshadri Sudha S Kurl Sudhir S Heckbert Susan R SR Ring Susan S Harris Tamara B TB Lehtimäki Terho T Galesloot Tessel E TE Shah Tina T de Faire Ulf U Plagnol Vincent V Rosamond Wayne D WD Post Wendy W Zhu Xiaofeng X Zhang Xiaoling X Guo Xiuqing X Saba Yasaman Y Dehghan Abbas A Seldenrijk Adrie A Morrison Alanna C AC Hamsten Anders A Psaty Bruce M BM van Duijn Cornelia M CM Lawlor Deborah A DA Mook-Kanamori Dennis O DO Bowden Donald W DW Schmidt Helena H Wilson James F JF Wilson James G JG Rotter Jerome I JI Wardlaw Joanna M JM Deanfield John J Halcox Julian J Lyytikäinen Leo-Pekka LP Loeffler Markus M Evans Michele K MK Debette Stéphanie S Humphries Steve E SE Völker Uwe U Gudnason Vilmundur V Hingorani Aroon D AD Björkegren Johan L M JLM Casas Juan P JP O'Donnell Christopher J CJ

Nature communications 20181203 1

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. Coloc ...[more]

PMID: 30510157

Similar Datasets

Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets