A1 Refereed original research article in a scientific journal
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
Authors: 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 LY, Scholz M, Sargurupremraj M, Pitkanen N, Franzen O, Joshi PK, Noordam R, Marioni RE, Hwang SJ, 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, Volzke H, Markus HS, Deary IJ, Jukema JW, de Graaf J, Price J, Pott J, Hopewell JC, Liang JJ, Thiery J, Engmann J, Gertow K, Rice K, Taylor KD, Dhana K, Kiemeney LALM, Lind L, Raffield LM, Launer LJ, Holdt LM, Dorr 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, Hagg S, Shah S, McLachlan S, Trompet S, Seshadri S, Kurl S, Heckbert SR, Ring S, Harris TB, Lehtimaki T, Galesloot TE, Shah T, de Faire U, Plagnol V, Rosamond WD, Post W, Zhu XF, Zhang XL, Guo XQ, Saba Y, 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, Lyytikainen LP, Loeffler M, Evans MK, Debette S, Humphries SE, Volker U, Gudnason V, Hingorani AD, Bjorkegren JLM, Casas JP, O'Donnell CJ, Humphries SE, Volker U, Gudnason V, Hingorani AD, Bjorkegren JLM, Casas JP, O'Donnell CJ
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 5141
Volume: 9
Number of pages: 14
ISSN: 2041-1723
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-07340-5
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/37280526
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.
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