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

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

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
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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