autism - genes and environment Flashcards
evidence for genes and ASD (3)
higher co-occurrence of ASD in MZ than DZ twins
first degree relatives have increased behavioural/cognitive features associated with ASD
–> the Broader Autism Phenotype
ASD co-occurs with genetic conditions
–> e.g. 16p11.2 and Sotos Syndrome
autism twin study + results
first twin study in 1977
Hallmayer et al (2011) found:
- 77% concordance in MZ
- 31% concordance in DZ
suggests genetic link - but don’t know what it is
autism as a spectrum
wide spread of data along an autism questionnaire - difference between diagnosed and undiagnosed
the broad autism phenotype
behavioural features of ASD (social interaction, friendships, pragmatics and speech) investigated in parents of:
- multi-incidence of autism families (MIAF)
- single-incidence of autism families (SIAF)
- families with children with Down’s syndrome
MIAF and SIAF parents showed increase in ASD related features
provides evidence for broad autism phenotype and genetic evidence for a genetic origin
sotos syndrome - characteristics and info
overgrowth syndrome
prevalence = 1/14,000
deletion on chromosome 5 - NSD1 gene
diagnostic criteria:
- overgrowth with advance bone age
- macrocephaly (large head circumference)
- characteristic facial appearance
- intellectual disability
sotos syndrome - study with autism
78 individuals with sotos syndrome
measured traits of autism using social responsiveness scale
83% scored above clinical cut off for ASD (had autism)
ASD co-occurrence with genetic conditions
e.g. sotos syndrome, fragile X syndrome, 16p11.2
supports idea of genetic association to ASD
some genes are more linked with ASD symptoms than others
complex genetics
- large number of genes - most likely interactions between them too
- ~65 genes linked to ASD - most likely involved in brain development
- single cause not known (and unlikely)
- but only 10-20% of ASD cases are accounted for by known genetic abnormality
- could it be that genes predispose and then there’s an external trigger
environmental epidemiology
observation of human populations infer the environmental causes of a condition or disease
bad scientific research with ASD - MMR vaccine
1998 - Wakefield et al - claimed link between MMR vaccine and autism
- only small sample of 12 children
- media repercussions - people choosing to not vaccinate kids - therefore more measles globally
- lack of trust around research on environmental causes of autism
MMR and autism - corrective study
paper was retracted due to evidence that parts were fraudulent
follow up studies have found no evidence for MMR vaccine and autism link (2019 study of 650,000 children)
environmental factors linked to autism (8)
- prenatal viral infection e.g. influenza, rubella ( depends on immune status of mother)
- maternal diabetes
- maternal obesity
- prenatal stress
- teratogens e.g. valproic acid (for epilepsy) or psychoactive drugs
- pesticide exposure in first 8 weeks of pregnancy
- parental age - advanced maternal age
- air pollution
NO CONCLUSIVE FACTORS KNOWN YET
issues with environment and autism
tricky to identify causes
using correlations - not causation
how to establish causality with environmental epidemiology - Hills criteria (9)
- temporality = effect after the cause
- consistency = similar findings in other contexts
- strength = of relationship between variables
- analogy = other similar relationships
- plausibility
- experiment = well designed and conducted observation
- biological gradient = greater exposure = greater incidence
- specificity = effect only found in relation to cause OR there is only one effect associated with the cause
- coherence = do findings match lab studies or well established relationships
environmental epidemiology research limitations
- observational research - not fully controlled
- records extraneous variables too
- results of one study are easily challenged
- confidence in results - meta-analysis used to make this stronger and see if relationships remain
example of contradiction:
suren et al (2013) - 85,176 children - folic acid during pregnancy reduced risk of autism
virk et al (2016) - 38,035 mothers - no evidence that folic acid reduces autism risk
air pollution and autism - meta-analysis
lam et al (2016)
screened set of papers with key words of autism and air pollution - fit inclusion criteria - reduced from 1,155 papers down to 23 suitable
exclusion = no original data, no human subjects, diagnosis of autism or definition of air pollution that wasn’t in line with PECO definition, no comparator group
particulate matter = small particles, used to mean air pollution
found small but significant association between particulate matter and ASD
odds ratios
odds ratio (OR)
statistical understanding of association between exposure and an outcome e.g. likelihood that cigarette smoking causes lung cancer
OR = 1 = exposure does NOT lead to an effect
OR < 1 = greater exposure is associated with less of an effect
OR > 1 = greater exposure is associated with larger effect
odds ratios showing risk of ASD from MMR vaccine
all datasets showed OR of <1 (all around 0.9)
therefore no association between MMR and ASD
conclusion: do environmental factors cause ASD
difficult to measure environmental exposure accurately
little evidence for environmental causes
possible suggestion to focus on particulate matter (pollution) as a risk factor
however - generally weak evidence for direct causal link between environment and ASD
gene-environment interaction in ASD
e.g. air pollution and MET gene
air pollution correlation with autism risk
MET gene (codes for proteins that trigger mitogenesis [cell division] and morphogenesis [ structural development] associated with autism risk
animal models - air pollution directly effects MET expression
shows 3 way link between gene, environment, and autism
ASD, MET, air pollution - study
Volk et al (2014)
- 252 autistic children + 156 neurotypical controls from Californian preschools
- MET genotype assessed via blood test
- exposure to air pollution measured for each
results:
interaction effect - children with both an alteration to MET gene and increased exposure to air pollution = increased risk of autism than those with just MET alteration or just increased air pollution exposure
therefore there is an interaction between genes and environment found
