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J Am Coll Cardiol. 2019 Jun 18;73(23):2932-2942. doi: 10.1016/j.jacc.2019.03.512.

Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases.

Author information

1
Clinical Pharmacology, William Harvey Research Institute, Barts and the London Medical School, Queen Mary University of London, London, United Kingdom; Centre for Genomic Health, Queen Mary University of London, London, United Kingdom.
2
Deutsches Herzzentrum München, Klinik für Herz und Kreislauferkrankungen, Technische Universität München, Munich, Germany.
3
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
4
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
5
Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; National Institute for Health Research Leicester Cardiovascular Biomedical Research Centre, Leicester, United Kingdom.
6
Clinical Pharmacology, William Harvey Research Institute, Barts and the London Medical School, Queen Mary University of London, London, United Kingdom; Centre for Genomic Health, Queen Mary University of London, London, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: p.deloukas@qmul.ac.uk.
7
Deutsches Herzzentrum München, Klinik für Herz und Kreislauferkrankungen, Technische Universität München, Munich, Germany; Deutsches Zentrum für Herz und Kreislauferkrankungen (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.

Abstract

BACKGROUND:

The taxonomy of cardiovascular (CV) diseases is divided into a broad spectrum of clinical entities. Many such diseases coincide in specific patient groups and suggest shared predisposition.

OBJECTIVES:

This study focused on coronary artery disease (CAD) and investigated the genetic relationship to CV and non-CV diseases with reported CAD comorbidity.

METHODS:

This study examined 425,196 UK Biobank participants to determine a genetic risk score (GRS) based on 300 CAD associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis.

RESULTS:

Hypercholesterolemia (odds ratio [OR]: 1.27; 95% CI: 1.26 to 1.29) and hypertension (OR: 1.11; 95% CI: 1.10 to 1.12) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. However, the CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR: 1.37; 95% CI: 1.30 to 1.44). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR: 1.28; 95% CI: 1.23 to 1.32), abdominal aortic aneurysms (OR: 1.28; 95% CI: 1.20 to 1.37), and stroke (OR: 1.08; 95% CI: 1.05 to 1.10), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR: 1.25; 95% CI: 1.22 to 1.29), atrial fibrillation (OR: 1.08; 95% CI: 1.05 to 1.10), and premature death (OR: 1.04; 95% CI: 1.02 to 1.06). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. Finally, an inverse association was observed between the score and migraine headaches (OR: 0.94; 95% CI: 0.93 to 0.96).

CONCLUSIONS:

A wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches.

KEYWORDS:

UK Biobank; cardiovascular diseases; coronary artery disease; genetic risk score; heart failure; migraine

PMID:
31196449
DOI:
10.1016/j.jacc.2019.03.512

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