Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07340-5
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Funding
- National Institute of Health [R21HL123677, R21-HL140385, DK104806-01A1, R01-MD012765-01A1]
- National Institutes of Health [R01HG009120, R01HG006399, U01CA194393, T32NS048004]
- American Heart Association [17POST33350042]
- British Heart Foundation [FS/14/55/30806]
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- German Federal Ministry of Education and Research (BMBF) in the context of the e:Med program (e:AtheroSysMed)
- DFG [CRC 1123]
- FP7/2007-2103 European Union project CVgenes@ target [Health-F2-2013-601456]
- NATIONAL CANCER INSTITUTE [U01CA194393] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL130114, R21HL123677, R01HL105756, T32HL129982, R21HL140385] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG009120, U41HG002273, R01HG006399] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R56DK104806, R01DK117445] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [U54GM115428] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [T32NS048004, R01NS017950, UH3NS100605] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [ZIAAG007380, R01AG054076, U01AG052409, ZIAAG000519] Funding Source: NIH RePORTER
- National Institute on Minority Health and Health Disparities [R01MD012765] Funding Source: NIH RePORTER
- British Heart Foundation [RG/13/16/30528] Funding Source: researchfish
- MRC [MC_UU_12015/1, MR/L003120/1, G1001245, MR/M006638/1, MR/K013351/1, G1001357, G0701120, MC_UU_12019/2, MR/R024227/1, MC_UU_12013/5, UKDRI-4002] Funding Source: UKRI
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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.
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