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Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease.

Lanktree MB, Hegele RA - Genome Med (2009)

Bottom Line: In addition, small-scale candidate gene association studies with functional hypotheses have identified gene-environment interactions.For future evaluation of gene-gene and gene-environment interactions to achieve the same success as the single gene associations reported in recent GWASs, it will be important to pre-specify agreed standards of study design and statistical power, environmental exposure measurement, phenomic characterization and analytical strategies.Here we discuss these issues, particularly in relation to the investigation and potential clinical utility of gene-gene and gene-environment interactions in CAD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departments of Medicine and Biochemistry, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, Canada.

ABSTRACT
Despite the recent success of genome-wide association studies (GWASs) in identifying loci consistently associated with coronary artery disease (CAD), a large proportion of the genetic components of CAD and its metabolic risk factors, including plasma lipids, type 2 diabetes and body mass index, remain unattributed. Gene-gene and gene-environment interactions might produce a meaningful improvement in quantification of the genetic determinants of CAD. Testing for gene-gene and gene-environment interactions is thus a new frontier for large-scale GWASs of CAD. There are several anecdotal examples of monogenic susceptibility to CAD in which the phenotype was worsened by an adverse environment. In addition, small-scale candidate gene association studies with functional hypotheses have identified gene-environment interactions. For future evaluation of gene-gene and gene-environment interactions to achieve the same success as the single gene associations reported in recent GWASs, it will be important to pre-specify agreed standards of study design and statistical power, environmental exposure measurement, phenomic characterization and analytical strategies. Here we discuss these issues, particularly in relation to the investigation and potential clinical utility of gene-gene and gene-environment interactions in CAD.

No MeSH data available.


Related in: MedlinePlus

The pathophysiology of coronary artery disease (CAD) is affected by environmental and genetic factors and their interactions. Pathogenic mechanisms contributing to plaque development and subsequent CAD can be affected both negatively and positively by environmental exposures and genes. Environmental exposures can be either discrete (presence or absence) or continuous. Typically, CAD associated mutations and polymorphisms are found in genes encoding proteins that have key roles in intermediate pathways. Neither the environmental nor genetic lists shown here are comprehensive.
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Figure 1: The pathophysiology of coronary artery disease (CAD) is affected by environmental and genetic factors and their interactions. Pathogenic mechanisms contributing to plaque development and subsequent CAD can be affected both negatively and positively by environmental exposures and genes. Environmental exposures can be either discrete (presence or absence) or continuous. Typically, CAD associated mutations and polymorphisms are found in genes encoding proteins that have key roles in intermediate pathways. Neither the environmental nor genetic lists shown here are comprehensive.

Mentions: Genetic investigations of coronary artery disease (CAD) aim to identify functional variants to assist with its diagnosis, prognosis or treatment. The full spectrum of DNA variant sizes and frequencies, ranging from single nucleotide changes to large copy number variations and from rare mutations to common polymorphisms, are components of a comprehensive approach to identify genetic determinants of CAD. However, CAD is the terminal manifestation of multiple intermediate disease processes, which individually have genetic and environmental determinants (Figure 1). For genetic research into CAD to be truly comprehensive, experimental methods must identify environmental and genetic factors and their interactions [1,2].


Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease.

Lanktree MB, Hegele RA - Genome Med (2009)

The pathophysiology of coronary artery disease (CAD) is affected by environmental and genetic factors and their interactions. Pathogenic mechanisms contributing to plaque development and subsequent CAD can be affected both negatively and positively by environmental exposures and genes. Environmental exposures can be either discrete (presence or absence) or continuous. Typically, CAD associated mutations and polymorphisms are found in genes encoding proteins that have key roles in intermediate pathways. Neither the environmental nor genetic lists shown here are comprehensive.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2664961&req=5

Figure 1: The pathophysiology of coronary artery disease (CAD) is affected by environmental and genetic factors and their interactions. Pathogenic mechanisms contributing to plaque development and subsequent CAD can be affected both negatively and positively by environmental exposures and genes. Environmental exposures can be either discrete (presence or absence) or continuous. Typically, CAD associated mutations and polymorphisms are found in genes encoding proteins that have key roles in intermediate pathways. Neither the environmental nor genetic lists shown here are comprehensive.
Mentions: Genetic investigations of coronary artery disease (CAD) aim to identify functional variants to assist with its diagnosis, prognosis or treatment. The full spectrum of DNA variant sizes and frequencies, ranging from single nucleotide changes to large copy number variations and from rare mutations to common polymorphisms, are components of a comprehensive approach to identify genetic determinants of CAD. However, CAD is the terminal manifestation of multiple intermediate disease processes, which individually have genetic and environmental determinants (Figure 1). For genetic research into CAD to be truly comprehensive, experimental methods must identify environmental and genetic factors and their interactions [1,2].

Bottom Line: In addition, small-scale candidate gene association studies with functional hypotheses have identified gene-environment interactions.For future evaluation of gene-gene and gene-environment interactions to achieve the same success as the single gene associations reported in recent GWASs, it will be important to pre-specify agreed standards of study design and statistical power, environmental exposure measurement, phenomic characterization and analytical strategies.Here we discuss these issues, particularly in relation to the investigation and potential clinical utility of gene-gene and gene-environment interactions in CAD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departments of Medicine and Biochemistry, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, Canada.

ABSTRACT
Despite the recent success of genome-wide association studies (GWASs) in identifying loci consistently associated with coronary artery disease (CAD), a large proportion of the genetic components of CAD and its metabolic risk factors, including plasma lipids, type 2 diabetes and body mass index, remain unattributed. Gene-gene and gene-environment interactions might produce a meaningful improvement in quantification of the genetic determinants of CAD. Testing for gene-gene and gene-environment interactions is thus a new frontier for large-scale GWASs of CAD. There are several anecdotal examples of monogenic susceptibility to CAD in which the phenotype was worsened by an adverse environment. In addition, small-scale candidate gene association studies with functional hypotheses have identified gene-environment interactions. For future evaluation of gene-gene and gene-environment interactions to achieve the same success as the single gene associations reported in recent GWASs, it will be important to pre-specify agreed standards of study design and statistical power, environmental exposure measurement, phenomic characterization and analytical strategies. Here we discuss these issues, particularly in relation to the investigation and potential clinical utility of gene-gene and gene-environment interactions in CAD.

No MeSH data available.


Related in: MedlinePlus