Simulating gene-environment interactions in complex human diseases 英文参考文献.docVIP

Peng Genome Medicine 2010,2:21 /content/2/3/21 MINIRE VIE W Simulating gene-environment interactions in complex human diseases Bo Peng* recent article by Amato and colleagues in BMC Bioin- Abstract formatics [4], which describes a mathematical model to Because little is currently known about how genes interact with environmental factors in human diseases, and because of the large number of possible interactions between and within genetic and environmental factors, it is dicult to simulate samples for a disease caused by multiple interacting genetic characterize gene-environment interactions (GxE) and a computer program that simulates them using biologically meaningful inputs. I evaluate the usefulness of the authors’ method for simulating samples with GxE for future studies. and environmental factors. A recent article by Amato and colleagues in BMC Bioinformatics describes a mathematical model to characterize gene-environment interactions and a computer program that simulates them using biologically meaningful inputs. Here, I evaluate the advantages and limitations of the authors’ approach in terms of its usefulness for simulating genetic samples for real-world studies of gene- environment interactions in complex human diseases. Specifying a GxE model for disease risk A disease model is needed before a sample can be simulated. If the number of genetic factors that cause a disease is G, we can denote each genetic factor by g i (where i = 1,…,G), and each of these will have three diploid genotypes. Similarly, with E environmental factors, we can denote these x , and each would have b possible j j discrete values (where j = 1,…,E). A complete GxE model would then have 3 G × Π E b possible items for each j=1 j combination of genetic and environmental factors. In addition, the model would require this same number of parameters to specify the risk associated with each