Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.
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PMID:Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder. 2721 46

Most of the genetic risk for autism spectrum disorder (ASD) is inherited as common genetic variants, although some rare mutations have been identified in individuals with ASD. Common genetic variants are most parsimoniously identified by genome wide association studies. Genome wide association studies have identified several genetic loci with genome wide association with ASD. However, genome wide association studies only identify regions of the genome associated with phenotypic traits. Identification of the functional elements requires additional experimental evidence. Here, we demonstrate that a genome wide association study locus for ASD on chromosome 20p12.1, rs4141463, implicates a noncoding RNA as a functional element. Although rs4141463 lies within an intron of the protein-coding MACROD2 (MACRO domain containing 2) gene, expression of MACROD2 is neither altered in postmortem temporal cortex of individuals with ASD nor correlated with rs4141463 genotype. Our bioinformatics approaches revealed a noncoding RNA transcript near the autism susceptibility signal, RPS10P2-AS1 (ribosomal protein S10 pseudogene 2 anti-sense 1). In a panel of 15 human tissues, RPS10P2-AS1 was expressed at higher levels than the protein-coding MACROD2 in both fetal temporal cortex and adult peripheral blood. In postmortem temporal cortex, expression of RPS10P2-AS1 was increased 7-fold in individuals with ASD (P = 0.02) and increased 8-fold in individuals with the ASD-associated rs4141463 genotype (P = 0.01). Further, RPS10P2-AS1 expression was increased in human neural progenitor cells exposed to model air pollutants, indicating that both genetic and environmental factors that contribute to ASD increased RPS10P2-AS1 expression. Overexpression of RPS10P2-AS1 in human neural progenitor cells indicated substantial changes in neuronal gene expression. These data indicate that genome-wide significant associations with ASD implicate long noncoding RNAs. Because long noncoding RNAs are more abundant in human brain than protein-coding RNAs, this class of molecules is likely to contribute to ASD risk.
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PMID:The Long Noncoding RNA RPS10P2-AS1 Is Implicated in Autism Spectrum Disorder Risk and Modulates Gene Expression in Human Neuronal Progenitor Cells. 3168 17

The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients.
Autism Res 2020 Nov 07
PMID:Expression Changes in Epigenetic Gene Pathways Associated With One-Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non-Typical Neurodevelopment. 3315 18