Diabetes mellitus susceptibility with varied diseased phenotypes and its comparison with phenome interactome networks

An emerging area of interest in understanding disease phenotypes is systems genomics. Complex diseases such as diabetes have played an important role towards understanding the susceptible genes and mutations. A wide number of methods have been employed and strategies such as polygenic risk score and allele frequencies have been useful, but understanding the candidate genes harboring those mutations is an unmet goal. In this perspective, using systems genomic approaches, we highlight the application of phenome-interactome networks in diabetes and provide deep insights. LINC01128, which we previously described as candidate for diabetes, is shown as an example to discuss the approach.     

Association of caspase9 promoter polymorphisms with the susceptibility of AML in south Indian subjects

Abnormal apoptosis is one of the hallmarks of cancers including acute myeloid leukemia (AML), as it plays a pivotal role in precisely maintaining self-renewal, proliferation, and differentiation properties of hematopoietic stem cells (HSCs). Caspase9 (CASP9), an initiator caspase activated by mitochondrial-mediated apoptotic pathway (intrinsic pathway), triggers cascade of effector caspases and executes apoptosis. Functional SNPs in CASP9 might influence the gene expression leading to altered apoptosis which confer the risk to AML. To test this hypothesis, we have analyzed four CASP9 gene polymorphisms [CASP9???1263A?>?G (rs4645978), CASP9???712C?>?T (rs4645981), CASP9???293_275del CGTGAGGTC AGTGCGGGGA (?293del) (rs4645982), and CASP9 Ex5?+?32G?>?A (rs1052576)] in 180 AML cases and 304 age- and sex-matched healthy controls. We performed various statistical analyses to determine the potential interactions between these SNPs and AML. The study revealed that presence of G allele at CASP9???1263 position elevates the risk of AML 1.53-fold and CT/TT genotype at CASP9???712 position by 2.60-fold under dominant model of inheritance. Two CASP9 haplotypes, G-del⁺-C-A and G-del⁺-T-A, were found to be significantly associated with increased AML risk by 2.19- (95 % confidence interval (CI), 1.09–4.39; p?=?0.028) and 11.75-fold (95 % CI, 1.01–136.57; p?=?0.05), respectively. Further, multidimensionality reduction (MDR) analysis had revealed single locus CASP9???712C?>?T SNP and four loci CASP9???1263A?>?G, CASP9???293del, CASP9???712C?>?T, and CASP9 Ex5?+?32G?>?A SNPs as highest predicting models for AML development. Our results revealed a significant association of two SNPs in CASP9 (?1263A?>?G and ?712C?>?T) and two haplotypes of the four SNP combinations with AML susceptibility.