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

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Franco Duran, Oscar Horacio

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Tanya Karrer

Date Deposited:

18 Dec 2018 11:11

Last Modified:

20 Dec 2018 12:23

Publisher DOI:

10.1038/s41467-018-07340-5

PubMed ID:

30510157

BORIS DOI:

10.7892/boris.122510

URI:

https://boris.unibe.ch/id/eprint/122510

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