For instance, transcription factor 7-like 2 (TCF7L2) and proteasome 26S subunit, non-ATPase 9 (PSMD9) are two genes independently reported as contributing to T2D and SCZ, and PSMD9 to MDD as well.
The transcription factor 7-like 2 (TCF7L2) gene confers one of the strongest genetic predispositions to type 2 diabetes, but diabetes development can be modified by diet.
Our results showed that generally, the TCF7L2 expression increase with a decrease in BMI, however, for patients with T2DM, it exhibits an inverse pattern, which is normalized one year after bariatric surgery.
Fine-mapping of the TCF7L2 locus suggested one type 2 diabetes association signal shared between Europeans and Africans (indexed by rs7903146) and a distinct African-specific signal (indexed by rs17746147).
Islet ATAC-seq peaks overlap with 13 SNPs associated with T2D (e.g. rs7903146, rs2237897, rs757209, rs11708067 and rs878521 near TCF7L2, KCNQ1, HNF1B, ADCY5 and GCK, respectively) and with additional 67 SNPs in LD with known T2D SNPs (e.g.
Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO.
In this first study of Arab descendants, we confirmed several known obesity (FTO, USP37, and RFX7), height (NSD1, MFAP2), and T2DM (TCF7L2, MC4R) associations; and report novel associations, like KCNK3 and RARB for T2DM.
Adult-onset, or type II diabetes mellitus (T2DM) has a complex genetic architecture, from hundreds of genes with low penetrance, common susceptibility variants (e.g., TCF7L2), to a set of more than ten genes that, when mutated, can cause a single-gene or Mendelian form of T2DM (e.g., GCK).
WGCNA showed that PLEKHA1 and TCF7L2 were interconnected with multiple osteoporosis and T2D associated genes in bone biopsy and pancreatic islets, such as JAG, EN1 and CPE.
Over 70% of genes mapping within type 2 diabetes-associated credible intervals showed peak differential expression during islet development, and type 2 diabetes GWAS loci of largest effect (including TCF7L2; log<sub>2</sub>FC = 1.2; q = 8.5 × 10<sup>-10</sup>) were notably enriched in genes differentially expressed at the posterior foregut stage (q = 0.002), as calculated by gene set enrichment analyses.
The rs7903146 T allele in transcription factor 7 like 2 (<i>TCF7L2</i>) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear.
We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (<i>TCF7L2</i>) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis.
In this cross-sectional study, the aim was to explore the association of genetic variants in CYP2C9, ABCC8, KCNJ11 and TCF7L2 with good glycaemic control in Mexican type 2 diabetes (T2D) treated with glibenclamide.
Interestingly one of the genes identified, catenin beta 1 (CTNNB1, β-catenin), is the key effector of the Wnt pathway and interacts with the nuclear receptor transcription factor 7-like 2 (TCF7L2), variants which are the most strongly associated with risk of developing T2D worldwide.
We performed a family study and determined if the T risk allele of the rs7903146 in the TCF7L2 gene increases the risk of type 2 diabetes based on real-time stable isotope measurements of insulin synthesis during an Oral Glucose Tolerance Test.