genes & environment in autism Flashcards
evidence for genetic involvement in autism
- higher co-occurrence of autism in MZ twins than DZ twins
- 1st degree relatives of autistic people have an increase in behavioural/cognitive features associated with autism
–> the broader autism phenotype - autism often co-occurs genetic conditions
–> e.g. 16p11.2
–. e.g. Sotos syndrome
twin studies in autism
- first twin study of autism was in 1997
- Hallmayer et al., (2011)
–> concordance rate of up to 77% in Mz twins
–> concordance rate of 31% in Dz twins
–> suggests there is a genetic link for autism but still don’t know what that is
autism as a spectrum
- not categorically yes or no
- there is a spectrum
- we are all on it to some extent, some people are towards the more extreme end of the spectrum
the broad autism phenotype
- behavioural features associated with autism 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 showed an increase in autism-related features
- considered to provide evidence for ‘Broad Autism Phenotype’
–> and also evidence for genetic origin of autism
Sotos syndrome
- “overgrowth” syndrome
- prevalence = 1 in 14,000
- deletions on chromosome 5 involving the NSD1 gene
- diagnostic criteria:
–> overgrowth with advanced bone age
–> macrocephaly
–> characteristic facial appearance
–> intellectual disability
Lane et al (2017) - Sotos syndrome
- recruited 78 individuals with Sotos syndrome
- measured traits of autism using the ‘Social Responsiveness Scale’
- found that 83% of participants scored above clinical cut-off for autism
co-occurrence of autism and other genetic conditions
- autism occurs in neurodevelopmental conditions with known genetic origin (e.g. Sotos syndrome, Fragile X syndrome, 16p11.2)
- highlights that genetic alterations are associated with autism symptoms, providing support for the argument that there is genetic association to autism
- some genes are more linked with autism symptoms than others
complex genetics
- involves a large number of different genes, and most likely interactions between different genes
- approx 65 different genes have been strongly linked to autism
–> genes are most involved in brain development - single genetic cause for autism is not known and very unlikely to exist
–> appears there are many genetic routes to autism - only 10%-20% of autism cases are accounted for by known genetic abnormality
environmental epidemiology
observation of human populations to infer the environmental causes of a condition or disease
environmental links to autism
- important to avoid unscientific reports in the media
- important to carry out good, rigorous science in an attempt to understand potential environmental causes of autism
- researchers recognise that environmental factors may contribute, in part, to the growing incidence of autism
example of bad science
- 1998, Wakefield et al. claimed that there was a link between the MMR vaccine
- paper was based on a very small sample of 12 children
- led to a media frenzy and to 1000s of people across the glob choosing not to vaccinate their children
- consequently more people are now contracting measles across the world
impact of Wakefield et al.’s work
- global increase in measles.
- lack of trust around research on environmental causes of autism
does the MMR vaccine cause autism?
- paper was later retracted as there was evidence that parts of the work were fraudulent
- many follow up studies have since found no evidence for a link between the MMR vaccine and autism
- in 2019, a paper found no evidence for a link between MMR and autism, in a population sample of over 650,000 children
environmental factors linked to autism
- prenatal viral infection (e.g. influenza or rubella)
–> effects are very dependent however on the immune status of the mother - maternal diabetes
- maternal obesity
- prenatal stress
- teratogens (e.g. valproic acid for epilepsy or psychoactive drugs)
- pesticide exposure during first 8 weeks of pregnancy
- parental age (advanced maternal age)
- air pollution
causation vs correlation
- incredibly tricky to identify clear environmental causes
- analysing environmental influences = correlations
- correlation does not equal causation
- drawing a direct line between cause and effect in a messy, complex world is inherently challenging
how can we try to establish causality? - Hill’s criteria
- strength
- temporality
- plausibility
- consistency
- biological gradient
- coherence
- experiment
- specificity
- analogy
environmental epidemiology
- environmental research is observational (not fully controlled)
- extraneous variables are also recorded
- results of one study are easily challenged
- how can we be confident in the results of our study?
–> meta-analyses
–> take numerous independent studies and combine their results to see if the relationship remains
evidence for folic acid in pregnancy and risk of autism
- Suren et al. (2013)
–> sample of 85,176 children
–> folic acid during pregnancy reduced risk of autism - Virk et al (2016)
–> sample of 38,035 mothers
–> no evidence that folic acid reduces the risk of autism
air pollution: meta analysis (Larn et al., 2016)
- initial set of papers are screened to identify relevant work that fits the inclusion criteria
- papers are whittled down until only the ones used are highly specific, trusted and original
- combined data shows a small but significant association between particulate matter (part of air pollution) and autism
Odds Ratios (OR)
- Odds Ratio provides a statistical method for understanding the association between exposure and an outcome
- ‘OR = 1’ means exposure to the cause does not lead to an effect
- ‘OR < 1’ means greater exposure to the cause is associated with LESS of an effect (good thing)
- ‘OR > 1’ means that greater exposure to the cause is associated with a LARGER effect (bad thing)
Odds Ratios and risk of autism from MMR
- ALL datasets showed odds ratio < 1
–> i.e. no association between MMR and autism
do environmental factors autism?
- measuring environmental exposure accurately is very difficult
- very little clear evidence for environmental causes of autism
- possible suggestions focus on particulate matter (air pollution) as a risk factor
- however evidence for a direct causal link between environmental factors and autism is generally weak
gene x environment interaction
genetic risk + environmental risk = increased likelihood of developmental condition (e.g. autism)
gene x environment interaction and autism
- some evidence for involvement of air pollution in autism risk
- one (of the many) genes that has been associated with increased risk of developing autism is the MET gene
–> the MET gene codes for proteins that trigger mitogenesis (cell division) and morphogenesis (structural development) - in animal models, air pollution has a direct effect on MET expression