👤 Rohit Saluja

Genetic factors are thought to play an important role in antipsychotic-induced weight gain (AIWG). This study conducted a meta-analysis of current research of the pharmacogenetic associations of adult AIWG. The analysis included papers providing comparisons of weight gain across at least two allele combinations for at least one single nucleotide polymorphism (SNP). Inclusion criteria were, patients 18 years of age or older and had received a diagnosis of severe mental illness, for which antipsychotic medication was prescribed. The association with AIWG needed to be replicated across at least two papers reporting separate sample sets. Two hundred twenty-three papers were assessed for eligibility. Of the 223 papers, 148 were excluded, leaving 75 studies to be included. Six SNPs in six different genes were identified as having significant associations ( The study identified six SNPs that predispose adult individuals to AIWG, with Show less

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, leading to premature cardiovascular disease (CVD). This study aimed to identify genetic variants associated with FH in patients from Telangana State, India. Probands with suspected FH were identified using the Dutch Lipid Clinic Network (DLCN) score, followed by cascade screening of their first-degree relatives. Targeted exome sequencing and pedigree analysis were performed to identify FH-associated genetic variants. We identified both novel and known high-impact mutations in genes implicated in FH pathogenesis, including stop-gain mutations in LPL (6/30; 20%) and LDLR (4/30; 13.3%), as well as splice donor site mutations in SLCO1B1 (1/30; 3.3%) and CETP (3/30; 10%). Notably, a novel frameshift mutation in LDLR was identified in two siblings (2/30; 6.7%), one of whom (50%) exhibited a homozygous variant and met the "Definite FH" classification based on the DLCN criteria. Additionally, moderate-impact variants rs2075291 (APOA5) and rs193922571 (LDLR) showed strong correlations with the DLCN score, suggesting increased susceptibility to FH. In contrast, rs6756629 (ABCG5) and rs11887534 (ABCG8) were strongly negatively correlated with LDL-C levels and the DLCN score, indicating potential protective effects against FH. These findings highlight the genetic heterogeneity of FH and emphasize the importance of identifying novel pathogenic variants. Moreover, the study underscores the role of moderate-impact variants in FH susceptibility. Overall, this research enhances our understanding of the genetic landscape of FH in the Indian population, with implications for improved diagnosis, risk assessment, and personalized management. Show less

Gallbladder cancer (GBC) is a common gastrointestinal malignancy noted for its aggressive characteristics and poor prognosis, which is mostly caused by delayed detection. However, the scarcity of information regarding somatic mutations in Indian patients with GBC has hampered the development of efficient therapeutic options. In the present study, the authors attempted to bridge this gap by revealing the mutational profile of GBC. To evaluate the somatic mutation profile, whole exome sequencing (WES) was performed on 66 tumor and matched blood samples from individuals with GBC. Somatic variant calling was performed using GATK pipeline. Variants were annotated at pathogenic and oncogenic levels, using ANNOVAR, VEP tools and the OncoKB database. Mutational signature analysis, oncogenic pathway analysis and cancer driver genes identification were performed at the functional level by using the maftools package. Our findings focused on the eight most altered genes with pathogenic and oncogenic mutations: TP53, SMAD4, ERBB3, KRAS, ARID1A, PIK3CA, RB1, and AXIN1. Genes with pathogenic single nucleotide variations (SNVs) were enriched in oncogenic signaling pathways, particularly RTK-RAS, WNT, and TP53 pathways. Furthermore, our research related certain mutational signatures, such as cosmic 1, cosmic 6, and cosmic 18, 29, to known characteristics including patient age and tobacco smoking, providing important insights into disease etiology. Given the scarcity of exome-based sequencing studies focusing on the Indian population, this study represents a significant step forward in providing a framework for additional in-depth mutational analysis. Genes with substantial oncogenic and pathogenic mutations are promising candidates for developing targeted mutation panels, particularly for GBC detection. Show less