rs1858830

This comprehensive review examines the genetic architecture of autism spectrum disorder (ASD), synthesizing research on risk genes, genetic variants, and signaling pathways. The paper discusses common variants linked at 5p14.1 and 5p15.2 loci (including rs4141463 at 20p12.1), copy number variations, rare mutations in syndromic autism genes, and the molecular mechanisms involving neuronal activity, synaptic plasticity, and key signaling pathways (Wnt, mTOR, BDNF, ERK/MAPK) that contribute to ASD pathophysiology. The authors emphasize that identification of ASD risk genes and biomarkers may facilitate early diagnosis and improve clinical treatments.

This study examined the association of the MET promoter variant rs1858830 C allele with autism spectrum disorder (ASD) phenotypes in 748 individuals from 367 families. The MET C allele was significantly associated with both social and communication phenotypes (p=0.008-0.001 across multiple instruments including ADI-R, ADOS, and SRS), particularly in families with co-occurring gastrointestinal conditions. Association was stronger in the dominant model (p=0.0008 for ASD diagnosis) compared to additive model, suggesting the C allele influences multiple domains of the autism triad.

A comprehensive review of the genetics of autism spectrum disorders, cataloging over 80% of autism cases involving detectable genetic changes from microarray analysis or whole exome sequencing. The paper organizes autism-associated genes by their roles in synaptic transmission and neural patterning, proposes that autism reflects inborn sensory nervous system deficits, and advocates for early genetic screening and sensory stimulation therapies during periods of neuroplasticity.

A comprehensive literature review examining the role of the human gut microbiome in health and disease. The paper discusses how dysbiosis (microbial imbalance) contributes to multiple diseases including Clostridium difficile infection, inflammatory bowel disease, celiac disease, obesity, colorectal cancer, and autism spectrum disorder. The review highlights gut microbiota-derived metabolites and their effects on host metabolism, immunity, and the nervous system, and examines therapeutic approaches including fecal microbiota transplantation and probiotics/prebiotics.

This study examined variants in five genes encoding proteins in the MET receptor tyrosine kinase signaling pathway (MET, HGF, PLAUR, SERPINE1, SP1, SUB1) in 664 autism spectrum disorder (ASD) families (2,712 individuals including 1,228 with ASD) and 312 controls. Family-based association testing confirmed that the MET rs1858830 C allele was significantly associated with ASD (P=0.008), with stronger evidence in multiplex families (P=0.001), and showed a relative risk of 1.76 (95% CI: 1.19-2.62) for CC genotype. The PLAUR promoter variant rs344781 T allele also showed significant association with ASD (FBAT P=0.006, case-control P=0.007) with relative risks of 1.93-2.42, and demonstrated functional relevance through luciferase assays. Other genes in the pathway showed no significant associations.