MacArthur et al. (2014) summarized several additional statistical checks including: rank the gene of interest with other genes (including non-disease-related genes) on the probability of being significant by chance, set type I error rates below 5% (1.7x10-6, 21,000 protein-coding genes and 9,000 long non-coding RNA genes (0.05/30,000)), test all of the variation in a gene together against a null model (considering sample size, gene size, and mutation rate; population specific), and replicate in independent samples. Sometimes, prioritizing and stratifying gene candidates can be used to boost power for gene discovery if pathogenicity or expression in tissues are better …show more content…
When TCF7L2 is knockout in mice, the crypt stem cells of the small intestine proliferated defectively and the knockout can be lethal for embryo. Also, the disruption of tcf7l2 in mice insulinoma cell line, and human pancreatic islets caused the downregulation of genes and proteins in the proinsulin pathway and the regulating processes. This suggests the role of TCF7L2 on regulating pancreatic Beta-cell function. Besides, Tcf7l2 is shown to be expressed in liver. If the gene is knockout in mice, the liver of the mice would be disrupted and Tcf7l2 was found to be overexpressed in the tissue. Studies also suggested that TCF7L2 might express in adipose tissue and brain, both are related to T2D. However, further research is needed to understand the potential influence of TCF7L2 on these