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

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 individu... Full description

Journal Title: Nature Communications Dec 2018, Vol.9, pp.1-14
Main Author: Franceschini, Nora
Other Authors: Giambartolomei, Claudia , de Vries, Paul , Finan, Chris , Bis, Joshua , Huntley, Rachael , Lovering, Ruth , Tajuddin, Salman , Winkler, Thomas , Graff, Misa , Kavousi, Maryam , Dale, Caroline , Smith, Albert , Hofer, Edith , van Leeuwen, Elisabeth , Nolte, Ilja , Lu, Lingyi , Scholz, Markus , Pitkänen
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 20411723 ; DOI: 10.1038/s41467-018-07340-5
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recordid: proquest2148974534
title: GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
format: Article
creator:
  • Franceschini, Nora
  • Giambartolomei, Claudia
  • de Vries, Paul
  • Finan, Chris
  • Bis, Joshua
  • Huntley, Rachael
  • Lovering, Ruth
  • Tajuddin, Salman
  • Winkler, Thomas
  • Graff, Misa
  • Kavousi, Maryam
  • Dale, Caroline
  • Smith, Albert
  • Hofer, Edith
  • van Leeuwen, Elisabeth
  • Nolte, Ilja
  • Lu, Lingyi
  • Scholz, Markus
  • Pitkänen
subjects:
  • Atherosclerosis
  • Stroke
  • Arteriosclerosis
  • Genes
  • Tissues
  • Genomes
  • Heart Diseases
  • Cardiovascular Diseases
  • Ischemia
  • Cardiovascular Disease
  • Heart
  • Regression Analysis
  • Carotid Artery
  • Stroke
  • Loci
  • Atherosclerosis
  • Regulatory Mechanisms (Biology)
  • Coronary Artery Disease
ispartof: Nature Communications, Dec 2018, Vol.9, pp.1-14
description: 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...
language: eng
source:
identifier: E-ISSN: 20411723 ; DOI: 10.1038/s41467-018-07340-5
fulltext: fulltext_linktorsrc
issn:
  • 20411723
  • 2041-1723
url: Link


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titleGWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
creatorFranceschini, Nora ; Giambartolomei, Claudia ; de Vries, Paul ; Finan, Chris ; Bis, Joshua ; Huntley, Rachael ; Lovering, Ruth ; Tajuddin, Salman ; Winkler, Thomas ; Graff, Misa ; Kavousi, Maryam ; Dale, Caroline ; Smith, Albert ; Hofer, Edith ; van Leeuwen, Elisabeth ; Nolte, Ilja ; Lu, Lingyi ; Scholz, Markus ; Pitkänen
ispartofNature Communications, Dec 2018, Vol.9, pp.1-14
identifierE-ISSN: 20411723 ; DOI: 10.1038/s41467-018-07340-5
subjectAtherosclerosis ; Stroke ; Arteriosclerosis ; Genes ; Tissues ; Genomes ; Heart Diseases ; Cardiovascular Diseases ; Ischemia ; Cardiovascular Disease ; Heart ; Regression Analysis ; Carotid Artery ; Stroke ; Loci ; Atherosclerosis ; Regulatory Mechanisms (Biology) ; Coronary Artery Disease
descriptionCarotid 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...
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titleGWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
descriptionCarotid 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...
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titleGWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
authorFranceschini, Nora ; Giambartolomei, Claudia ; de Vries, Paul ; Finan, Chris ; Bis, Joshua ; Huntley, Rachael ; Lovering, Ruth ; Tajuddin, Salman ; Winkler, Thomas ; Graff, Misa ; Kavousi, Maryam ; Dale, Caroline ; Smith, Albert ; Hofer, Edith ; van Leeuwen, Elisabeth ; Nolte, Ilja ; Lu, Lingyi ; Scholz, Markus ; Pitkänen
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10Heart
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98Rauramaa, Rainer
99Burkhardt, Ralph
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genrearticle
ristypeJOUR
abstractCarotid 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...
copLondon
pubNature Publishing Group
doi10.1038/s41467-018-07340-5
urlhttp://search.proquest.com/docview/2148974534/
orcidid0000-0001-6718-3559
issue1
oafree_for_read
date2018-12-01