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

Shah T; Thiery J; Giral P; Lind L; Wilson JF; Franco OH; Smit AJ; Sitzer M; Campbell H; Strawbridge RJ; Winkler TW; Volzke H; Nalls MA; Lyytikainen LP; Schminke U; Galesloot TE; Evans MK; Veglia F; de Vries PS; Price J; van Duijn CM; Wassel CL; Heckbert SR; Rotter JI; Loeffler M; Lehtimaki T; Markus HS; Pott J; O'Leary DH; Kurl S; Launer LJ; Mannarino E; Isaacs A; Hwang SJ; Lu LY; Zonderman AB; Humphries SE; Sargurupremraj M; Grossi E; Graff M; de Faire U; Newman AB; Saba Y; Post W; Liang JJ; Hofman A; Bis JC; Morris RW; Penninx BW; O'Donnell CJ; Schmidt H; Snieder H; Dichgans M; Kavousi M; Heiss G; Anugu P; Nolte IM; Uitterlinden AG; Schadt EE; Volker U; Wardlaw JM; Kuh D; Gertow K; Joshi PK; Tzourio C; Taylor KD; Langefeld CD; Amouyel P; Deanfield J; Ingelsson E; Zhu XF; Rice K; Holdt LM; Teupser D; Engmann J; Hagg S; Schmidt R; Whincup PH; Roussos P; Tremoli E; Kumari M; Zhang XL; Dhana K; McLachlan S; Marioni RE; Plagnol V; Boerwinkle E; Pitkanen N; Raitakari O; Rivadeneira F; Franzen O; Kivimaki M; Tajuddin SM; Hamsten A; Jukema JW; Seldenrijk A; Dorr M; Wilson JG; Finan C; Melander O; Correa A; Psaty BM; Wannamethee SG; Hopewell JC; Fava C; Beutner F; Franceschini N; Guo XQ; Rosamond WD; Harris TB; Giambartolomei C; Wong A; Chauhan G; Lawlor DA; de Mutsert R; Cox AJ; Pasaniuc B; Halcox J; Kiemeney LALM; Traylor M; Hingorani AD; Casas JP; Britton A; Noordam R; de Graaf J; Dale C; Baldassarre D; Raffield LM; Ruusalepp A; Wong Q; Deary IJ; Lovering RC; Mook-Kanamori DO; Dehghan A; Trompet S; Sennblad B; Bjorkegren JLM; Rauramaa R; Shah S; Teumer A; Hardy R; Burkhardt R; Morrison AC; Scholz M; Seshadri S; Debette S; Palmas W; Rueda-Ochoa OL; Hedblad B; Ring S; Bowden DW; Hofer E; Huntley RP; Malik R; Musani SK; Gudnason V; Smith AV; van Leeuwen EM
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Shah T
Thiery J
Giral P
Lind L
Wilson JF
Franco OH
Smit AJ
Sitzer M
Campbell H
Strawbridge RJ
Winkler TW
Volzke H
Nalls MA
Lyytikainen LP
Schminke U
Galesloot TE
Evans MK
Veglia F
de Vries PS
Price J
van Duijn CM
Wassel CL
Heckbert SR
Rotter JI
Loeffler M
Lehtimaki T
Markus HS
Pott J
O'Leary DH
Kurl S
Launer LJ
Mannarino E
Isaacs A
Hwang SJ
Lu LY
Zonderman AB
Humphries SE
Sargurupremraj M
Grossi E
Graff M
de Faire U
Newman AB
Saba Y
Post W
Liang JJ
Hofman A
Bis JC
Morris RW
Penninx BW
O'Donnell CJ
Schmidt H
Snieder H
Dichgans M
Kavousi M
Heiss G
Anugu P
Nolte IM
Uitterlinden AG
Schadt EE
Volker U
Wardlaw JM
Kuh D
Gertow K
Joshi PK
Tzourio C
Taylor KD
Langefeld CD
Amouyel P
Deanfield J
Ingelsson E
Zhu XF
Rice K
Holdt LM
Teupser D
Engmann J
Hagg S
Schmidt R
Whincup PH
Roussos P
Tremoli E
Kumari M
Zhang XL
Dhana K
McLachlan S
Marioni RE
Plagnol V
Boerwinkle E
Pitkanen N
Raitakari O
Rivadeneira F
Franzen O
Kivimaki M
Tajuddin SM
Hamsten A
Jukema JW
Seldenrijk A
Dorr M
Wilson JG
Finan C
Melander O
Correa A
Psaty BM
Wannamethee SG
Hopewell JC
Fava C
Beutner F
Franceschini N
Guo XQ
Rosamond WD
Harris TB
Giambartolomei C
Wong A
Chauhan G
Lawlor DA
de Mutsert R
Cox AJ
Pasaniuc B
Halcox J
Kiemeney LALM
Traylor M
Hingorani AD
Casas JP
Britton A
Noordam R
de Graaf J
Dale C
Baldassarre D
Raffield LM
Ruusalepp A
Wong Q
Deary IJ
Lovering RC
Mook-Kanamori DO
Dehghan A
Trompet S
Sennblad B
Bjorkegren JLM
Rauramaa R
Shah S
Teumer A
Hardy R
Burkhardt R
Morrison AC
Scholz M
Seshadri S
Debette S
Palmas W
Rueda-Ochoa OL
Hedblad B
Ring S
Bowden DW
Hofer E
Huntley RP
Malik R
Musani SK
Gudnason V
Smith AV
van Leeuwen EM
Katso/Avaa
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NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-07340-5
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042720504
Tiivistelmä
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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