PHG Foundation | Large-scale research into heart disease genetics

Large-scale research into heart disease genetics
Analysis of a study published in a science journal | By Dr Gurdeep Sagoo | Published 14 October 2010

Study: Design of the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) study - a genome-wide association meta-analysis involving more than 22,000 cases and 60,000 controls
By: Preuss M. et al. (38 authors total)
In: Circulation: Cardiovascular Genetics
Link: http://dx.doi.org/10.1161/CIRCGENETICS.109.899443

What this study set out to do:

In order to increase the statistical power to detect genetic variants with small effect sizes on coronary artery disease (CAD) and myocardial infarction (MI), the authors formed a large consortium in order to pool data across several studies.

How they went about it:

CARDIoGRAM combined data from all published and unpublished GWAS individuals with European ancestry – including more than 22,000 cases and 60,000 controls – across several studies investigating coronary artery disease and/or myocardial infarction. The results from each study were combined using meta-analysis.
Outcome:

As a proof-of-principle analysis, the study authors chose to replicate three SNPs on chromosome 9p21 - all previously found to be associated with CAD/MI – along with another SNP on 9p21 associated with type 2 diabetes not CAD. Results were in agreement with earlier findings.

Conclusion:

The study authors state that this newly-formed consortium has increased the sample size by a factor of 10 for cases and 20 for controls over previously published GWAS studies. This in turn increases the statistical power to detect true associations of small effect sizes. The authors hope that this dataset will be utilised by the research community to improve understanding of the role of common genetic variation on risk for CAD and MI.

Our view:

The consortium authors acknowledge that using only individuals with European ancestry will largely limit the findings to that population group. However, they hope that by providing a large number of validated loci in this population, the research community can then investigate these in non-European populations. At the same time, the consortium dataset can be used to test loci identified in non-European populations in a large European dataset.

Of interest will be the potential planned use of the increased statistical power with this dataset to shed further light on the causal nature of several biomarkers and other intermediate traits on CAD and MI.
Keywords: Disease Susceptibility (Genetic)
PHG Foundation | Large-scale research into heart disease genetics