A systematic review of common genetic variation and biological pathways in autism spectrum disorder

Abstract

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social communication and interaction. Common genetic variation appears to play a key role in the development of this condition. In this systematic review, we describe the relationship between genetic variations and autism. We created a gene dataset of the genes involved in the pathogenesis of autism and performed an over-representation analysis to evaluate the biological functions and molecular pathways that may explain the associations between these variants and the development of ASD. Results 177 studies and a gene set composed of 139 were included in this qualitative systematic review. Enriched pathways in the over-representation analysis using the KEGG pathway database were mostly associated with neurotransmitter receptors and their subunits. Major over-represented biological processes were social behavior, vocalization behavior, learning and memory. The enriched cellular component of the proteins encoded by the genes identified in this systematic review were the postsynaptic membrane and the cell junction. Conclusions Among the biological processes that were examined, genes involved in synaptic integrity, neurotransmitter metabolism, and cell adhesion molecules were significantly involved in the development of autism.

Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study

“…The two most common NDDs among children are attention-deficit/hyperactivity disorder (ADHD) diagnosed in 5-10% and autism diagnosed among 1-3%, of children globally [2][3][4]. Several of the risk factors are known including (epi-)genetic, environmental, and psychosocial factors including pre-and perinatal factors such as preterm birth, pollutants, dietary factors and parental characteristics (obesity, age)-yet familial confounding makes it difficult to establish independent effects [2][3][4][5]. However, evidence indicates that exposure to systemic antibiotics during the developmental phase (and in early life) may pose a risk factor for these disorders through mechanisms grounded in the gut microbiome [6,7].…”

Variation in glutamate and GABA genes and their association with brain structure and chemistry in autism

“…A study comparing four animal models for autism confirmed an increased E/I ratio due to hyperexcitability and reduced feedforward inhibition (62). A recent systematic review focusing on common genetic variation in autism also confirmed alterations in genes involved in the synthesis of GABA-A receptors as well as both ionotropic and metabotropic glutamate receptors (63). Here we showed that genetic variation was associated with glutamate concentrations in the ACC, a region implicated in autism and related phenotypes (64)(65)(66) as well as a region where glutamate concentrations have consistently been reported to be associated with autism before (7,8,23,67).…”

Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder

“…The gene that encodes TPH , a rate-limiting enzyme for 5-HT synthesis, has been associated with ASD and other neurological disorders [ 223 , 224 ]. Moreover, a systematic review of common genetic variation in ASD showed that enriched pathways in the over-representation analysis are mostly associated with neurotransmitter receptors and their subunits, including 5-HT, GABA, and glutamate receptors [ 225 ]. During brain development, 5-HT has been shown to modulate numerous events, including cell division, neuronal migration, cell differentiation, and synaptogenesis, even before it becomes important as a neurotransmitter [ 226 , 227 ].…”