Genetics of coronary artery disease: discovery, biology and clinical translation View Full Text


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Article Info

DATE

2017-03-13

AUTHORS

Amit V. Khera, Sekar Kathiresan

ABSTRACT

Key PointsCoronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics. More... »

PAGES

331-344

References to SciGraph publications

  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2013-10-06. Discovery and refinement of loci associated with lipid levels in NATURE GENETICS
  • 2008-01-13. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans in NATURE GENETICS
  • 2008-01-13. Newly identified loci that influence lipid concentrations and risk of coronary artery disease in NATURE GENETICS
  • 2013-05-29. The Genotype-Tissue Expression (GTEx) project in NATURE GENETICS
  • 2008-01-06. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm in NATURE GENETICS
  • 2006-02-07. Genetic susceptibility to coronary artery disease: from promise to progress in NATURE REVIEWS GENETICS
  • 2012-12-02. Large-scale association analysis identifies new risk loci for coronary artery disease in NATURE GENETICS
  • 2016-09-12. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals in NATURE GENETICS
  • 2014-07-22. Biological insights from 108 schizophrenia-associated genetic loci in NATURE
  • 2015-09-07. A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease in NATURE GENETICS
  • 2016-07-11. Type 2 diabetes: genetic data sharing to advance complex disease research in NATURE REVIEWS GENETICS
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2009-02-08. New susceptibility locus for coronary artery disease on chromosome 3q22.3 in NATURE GENETICS
  • 2009-02-08. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants in NATURE GENETICS
  • 2014-04-23. Guidelines for investigating causality of sequence variants in human disease in NATURE
  • 2016-03-14. The genetics of drug efficacy: opportunities and challenges in NATURE REVIEWS GENETICS
  • 2003-05-05. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia in NATURE GENETICS
  • 2013-11-10. Dysfunctional nitric oxide signalling increases risk of myocardial infarction in NATURE
  • 2012-01-18. Rare and common variants: twenty arguments in NATURE REVIEWS GENETICS
  • 2011-02-09. 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response in NATURE
  • 2015-01-28. New loci and coding variants confer risk for age-related macular degeneration in East Asians in NATURE COMMUNICATIONS
  • 2011-03-06. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease in NATURE GENETICS
  • 2014-12-10. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction in NATURE
  • 2016-02-15. Unravelling the human genome–phenome relationship using phenome-wide association studies in NATURE REVIEWS GENETICS
  • 2005-01-16. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 in NATURE GENETICS
  • 2010-08. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus in NATURE
  • 2010-02-19. How to improve R&D productivity: the pharmaceutical industry's grand challenge in NATURE REVIEWS DRUG DISCOVERY
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2016-05-03. Developing and evaluating polygenic risk prediction models for stratified disease prevention in NATURE REVIEWS GENETICS
  • 2008-09-21. Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development in NATURE MEDICINE
  • 2013-07-19. Validating therapeutic targets through human genetics in NATURE REVIEWS DRUG DISCOVERY
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    43 schema:description Key PointsCoronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics.
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