title: [Genetic, environmental, and epigenetic contribution to the susceptibility to autism spectrum disorders].
abstract: BACKGROUND
  Autism spectrum disorders (ASD) are common and complex neuropsychiatric disorders in which multiple factors may contribute to the phenotype.
  
  
  OBJECTIVE
  To review current knowledge about possible risk factors for ASD.
  
  
  METHODS
  Medline, OMIM and Ensembl databases were searched for possible risk factors, disease and gene information.
  
  
  CONCLUSIONS
  There is genetic heterogeneity and probably different modes of transmission in ASD. In addition, many cases are related with non-inherited de novo mutations or uncommon alleles with a large effect. The general heritability in these disorders may be lower than previously reported. Some fraction of it may be explained by relatively common alleles that tend to have a small effect. To some extent, susceptibility alleles may have a different influence on the phenotype depending on other genetic or non-genetic factors. Non-genetic factors in the perinatal and postnatal period, including epigenetics, the age of the father and possibly the age of grandparents at conception may be relevant for ASD. The mechanisms involved in the etiology of ASD may be related with synaptic development and connectivity, neurotransmission, signaling, neuroplasticity, and gene expression. Different methods have contributed to understand the etiology of ASD. Linkage and association studies are not appropriate for ASD cases with de novo mutations with a strong effect. The observed increase in ASD prevalence may be related not only with more awareness, changing diagnostic criteria, and environmental exposures, but also with epigenetic changes, and an increasing number of de novo mutations.
authors.affiliation: Instituto Nacional de Psiquiatria Ramon de la Fuente Muniz, 14370 Mexico DF, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Díaz-Anzaldúa
authors.forename: Alejandro
authors.initials: A
authors.lastname: Díaz-Martínez
mesh_terms: D000328:Adult; D000818:Animals; D015551:Autoimmunity; D001921:Brain / Q000196:embryology / Q000503:physiopathology; D002659:Child Development Disorders, Pervasive / Q000209:etiology* / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004781:Environmental Exposure; D044127:Epigenesis, Genetic; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity; D010331:Paternal Age; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D009435:Synaptic Transmission; D018433:Twin Studies as Topic
chemical_list: D009419:Nerve Tissue Proteins