cell type abundance might differ between cases and controls. Further, the acquisition of some types of tissues (for example, brain) is almost entirely limited to postmortem specimens, introducing additional confounding parameters like the cause of death and the delay in the dissection of the tissue, which could lead to RNA degradation. Many studies attempt to bypass such limitations by examining lymphocytes or immortalized cell lines that are often readily available or easy to acquire. This reduces significant sources of variation, however it might be of limited value for the study of a psychiatric disease. Although it can be argued that some of the gene expression differences will be similar in brain and lymphocytes, only a fraction of genes will be expressed in both tissues and those are likely to be subject to different regulatory mechanisms in tissues that have different functions. Many other limitations including alternative splicing, environmental factors like diet and drugs, as well as platform-specific characteristics introduce additional levels of complexity and highlight the importance of careful experimental design in GWGE studies.
