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Risk Factors for Autism - Coggle Diagram

- - - - Baby-sibling designs
        
        Prospective research design
        
        MZ twins (96%) > DZ twins (27%)
        
        Sibling recurrence risk ~19%
      - Broader Autism Phenotype (BAP) -
        
        subthreshold ASD-like traits; insufficient to reach diagnostic criteria
        
        siblings and parents at increased risk
        
        high heritability - ASD susceptibility genes?
        
        h2 = 2(Rmz - Rdz)
      - Suggests that ASD has a significant heritable contribution, but it is not fully penetrant
        
        Both genetic and environmental influences
    - - Family-based analysis to identify genome regions linked to ASD - finding high-impact variants and/or susceptibility genes
        
        Comparing and contrasting the genes of two siblings, one with and one without ASD
        
        Looking for genetic markers consistently inherited in family members with ASD
        
        Simplex - de novo mutations
        Multiplex - subclinical autistic traits and genetic transmission
    - - Statistical associations between single nucleotide polymorphisms (SNPs)
        
        SNP - small but frequent differences in genetics across the population
        
        SNP - small but frequent differences
        CNV - large and rare differences
        
        Identifying SNPs that may influence the development of ASD
        
        Limited success so far
  - - - CNVs
        
        structural variants in larger genome portions - more significant changes in gene function/expression/coding
        
        more frequently observed in ASD (rare de novo CNVs in 15-20% of ASD cases - Devlin & Scherer (2012)
        
        DNA deletion - reduced expression/loss of function
        
        DNA duplication - overexpression/potential imbalance
        
        DNA translocation - unregular gene expression
        
        Can disrupt brain development, neuronal connectivity, and synaptic function
      - Up to 15% of cases - due to known genetic mutation
        Most are due to multiple gene abnormalities
    - - Fragile X, Tuberous Sclerosis Complex, Neurofibromatosis
- - - - Low, but consistent
  - - - BPA, phthalates, pesticides, hazardous air pollutants (HAP) - De Cook et al. (2013)
    - - Thalidomide (nausea in pregnancy) - 50X ASD risk increase
      - Valproic acid (anti-epileptic) - 8-18X ASD risk increase
      - Alcohol - mixed results
      - Antidepressants
  - - - Greater risk for East Asian mothers
  - - - Paternal ageing - higher frequency of point mutations, genetic changes in sperm, de novo CNVs
      - Maternal ageing - chromosomal imbalance
- - - - Risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females - Muller et al. (2017)
      - Social behavior, cognitive flexibility, sensory development, digestion
  - - - Increased GM volume of frontal and temporal lobes
        
        Frontal cortex - delayed maturation
        
        Could be reflected in EF deficits and the EF theory of autism
      - Decreased GM volume in temporal/ parietal lobes (social cognition)
    - - Reduced WM connectivity for social behaviour, language, and sensory processing
      - Corpus callosum less developed - impaired cross-hemisphere integration