four things you should know about environmental autism...
TRANSCRIPT
Craig NewschafferDirector, AJ Drexel Autism Institute
Drexel University
Four things you should know about environmental autism risk factors
Outline
What is a “risk factor”
What is “environment”① Environmental risk factors do contribute to causing
autism
② Environmental risk factors are challenging for scientists to discover and confirm
③ The amount of increased risk any one environmental risk factor conveys to the individual is likely quite small
④ However, the overall impact in the population can be quite large
Environmental risk factors with supporting evidence under study now
Time for questions
What is a “risk factor”?
Something that affects the chance of an outcome
chance = probability
…so, there is some math thinking involved.
What does a 30% chance of rain mean?
What is a “the environment”?
Everything that is not heritable…
① Environmental risk factors do contribute to causing autism
① Environmental risk factors do contribute to causing autism
Family studies contrast recurrence of a condition among family members of different known “relatedness” to estimate heritability
Autism twin studies
Heritability estimates from modern twin studiestend to be 50%-60%, with some (higher) exceptions
Other recent family studies generated higher (>80%) heritability estimates
GENES
ENVIRONMENT
Multifactorial causation
Z YS
TU V
X
W
① Environmental risk factors do contribute to causing autism
Single factor causation
G
① Environmental risk factors do contribute to causing autism
Gene-environment interaction
G E
① Environmental risk factors do contribute to causing autism
Gene-environment interaction
G E
Heritability in family studies is over-estimated
① Environmental risk factors do contribute to causing autism
Dev Med Child Neurol, 1994
Stromland et al. Dev Med Child Neurol 1994
Proof of principle exposure example
① Environmental risk factors do contribute to causing autism
② Environmental risk factors are challenging for scientists to discover and confirm
The environment is everything that is not heritable…
② Environmental risk factors are challenging for scientists to discover and confirm
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
However<20% detectable chemicals adequately screened for neurodevelopmental effects
3,000 high volumechemicals
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
However<20% detectable chemicals adequately screened for neurodevelopmental effects
80,000 new synthesized chemicals
3,000 high volumechemicals
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
However<20% detectable chemicals adequately screened for neurodevelopmental effects
Source: Yuen et al. Nat Neurosci 2018
② Environmental risk factors are challenging for scientists to discover and confirm
Interrogation of the whole genome (genomics) is now common
② Environmental risk factors are challenging for scientists to discover and confirm
Interrogation of the whole “exposome” in its earliest days
Rappaport and Smith, Science 2010
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Risk ratio = 1.9
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Risk ratio = 1.9(1.9 = 2.7% / 1.5%)
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Prenatal SSRI absent
1.5%
Risk ratio = 1.9
Prenatal SSRI present
2.7%
(1.9 = 2.7% / 1.5%)
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Prenatal SSRI absent
1.5%
Risk ratio = 1.9
Prenatal SSRI present
2.7%
1.2% absolute differencein risk
(1.9 = 2.7% / 1.5%)
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
④ However, the overall impact in the population can be quite large
④ However, the overall impact in the population can be quite large
Risk ratio = 2.3 for each standard deviation of PM2.5
④ However, the overall impact in the population can be quite large
Risk ratio = 2.3 for each standard deviation of PM2.5
(2.3 = 3.5% / 1.5%)
④ However, the overall impact in the population can be quite large
One SD belowthe mean
1.5%
Risk ratio = 2.3 for each standard deviation of PM2.5
One SD abovethe mean
3.5%
(2.3 = 3.5% / 1.5%)
④ However, the overall impact in the population can be quite large
One SD belowthe mean
1.5%
Risk ratio = 2.3 for each standard deviation of PM2.5
One SD abovethe mean
3.5%
2% absolute differencein risk
(2.3 = 3.5% / 1.5%)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
ASDprevalence
8.5%
ASDprevalence
0.1%
Risk ratio = 2.3 for each standard deviation of PM2.5
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
Population ASD prevalence down from 1.5% to 1.4% (3% reduction in ASD cases in the population overall)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
Population ASD prevalence down from 1.5% to 0.8% (47% reduction in ASD cases in the population)
④ However, the overall impact in the population can be quite large
Specific environmental risk factors with supporting evidence under study now
• Parental age• Pre-, peri-, and neonatal
complications– Low birth weight / SGA– Infection
• Prenatal medication use• Short interpregnancy interval• Prenatal (preconception) nutrition
– Folate • Prenatal (preconception) air
pollution• Endocrine disrupting chemicals
www.prhe.ucsf.edu/info
www.drexel.edu/[email protected]
QUESTIONS?