International Journal of Epidemiology 2002;31:730-736
© International Epidemiological Association 2002
Review |
Genetic epidemiological studies of coronary heart disease
Institute of Human Genetics and Department of Cardiology, University of Newcastle-upon-Tyne, UK.
Dr Bernard Keavney, Institute of Human Genetics, Central Parkway, Newcastle-upon-Tyne NE1 3BZ, UK. E-mail: b.d.keavney@ncl.ac.uk
Keywords Coronary heart disease, genetics
Accepted 26 March 2002
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Introduction |
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The recent publication of the human genome sequence is widely thought to offer the opportunity for a radical change in our understanding of a variety of common human diseases. One particular hope is that the new information available from the genome sequencing effort will facilitate the conduct of population genetic studies, which will discover the genetic variants responsible for ‘complex’ or ‘polygenic’ (i.e. resulting from the action of more than one gene) diseases. In this review I attempt to put this aspiration into perspective for coronary heart disease (CHD). Firstly, I consider what is known thus far regarding the ‘genetic architecture’ of CHD. Secondly, I discuss the implications of this ‘genetic architecture‘, and of certain population genetic issues, for study design. Thirdly, I consider the reasons why the results of genetic-epidemiological studies of CHD to date have tended to be discrepant, and explore strategies for increasing the reliability of such
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How large is the genetic contribution to CHD risk? |
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How many genes? |
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How many alleles? |
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Case-control genetic association studies of CHD |
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Linkage disequilibrium: islands in a stream of variation? |
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Candidate genes or ‘large hypothesis’ approach? |
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Why have results thus far been so unreliable? |
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Genetic associations as a test for causality |
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Conclusions |
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