Four things you should know about environmental autism risk factors. Craig Newschaffer Director, AJ Drexel Autism Institute Drexel University

Transcription

1 Four things you should know about environmental autism risk factors Craig Newschaffer Director, AJ Drexel Autism Institute Drexel University

2 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

3 What is a risk factor? Something that affects the chance of an outcome chance = probability so, there is some math thinking involved.

4 What does a 30% chance of rain mean?

5 What is a the environment? Everything that is not heritable

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7 1 Environmental risk factors do contribute to causing autism

8 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 studies tend to be 50%-60%, with some (higher) exceptions Other recent family studies generated higher (>80%) heritability estimates

9 GENES ENVIRONMENT

10 1 Environmental risk factors do contribute to causing autism Multifactorial causation T S U Z V Y W X

11 1 Environmental risk factors do contribute to causing autism Single factor causation G

12 1 Environmental risk factors do contribute to causing autism Gene-environment interaction G E

13 1 Environmental risk factors do contribute to causing autism Gene-environment interaction G E Heritability in family studies is over-estimated

14 1 Environmental risk factors do contribute to causing autism Proof of principle exposure example Dev Med Child Neurol, 1994 Stromland et al. Dev Med Child Neurol 1994

15 2 Environmental risk factors are challenging for scientists to discover and confirm

16 2 Environmental risk factors are challenging for scientists to discover and confirm The environment is everything that is not heritable

17 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

18 2 Environmental risk factors are challenging for scientists to discover and confirm 8-10 synthesized chemicals proven as developmental neurotoxicants 200 detected in blood/urine of all Americans Source: Landrigan and Goldman Health Aff 2012

19 2 Environmental risk factors are challenging for scientists to discover and confirm 8-10 synthesized chemicals proven as developmental neurotoxicants However<20% detectable chemicals adequately screened for neurodevelopmental effects 200 detected in blood/urine of all Americans Source: Landrigan and Goldman Health Aff 2012

20 2 Environmental risk factors are challenging for scientists to discover and confirm 8-10 synthesized chemicals proven as developmental neurotoxicants However<20% detectable chemicals adequately screened for neurodevelopmental effects 200 detected in blood/urine of all Americans 3,000 high volume chemicals Source: Landrigan and Goldman Health Aff 2012

21 2 Environmental risk factors are challenging for scientists to discover and confirm 8-10 synthesized chemicals proven as developmental neurotoxicants However<20% detectable chemicals adequately screened for neurodevelopmental effects 200 detected in blood/urine of all Americans 3,000 high volume chemicals 80,000 new synthesized chemicals Source: Landrigan and Goldman Health Aff 2012

22 2 Environmental risk factors are challenging for scientists to discover and confirm Interrogation of the whole genome (genomics) is now common Source: Yuen et al. Nat Neurosci 2018

23 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

24 3 The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

25 3 The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

26 3 The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small Risk ratio = 1.9

27 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%)

28 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%) 1.5% Prenatal SSRI absent 2.7% Prenatal SSRI present

29 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%) 1.2% absolute difference in risk 1.5% Prenatal SSRI absent 2.7% Prenatal SSRI present

30 4 However, the overall impact in the population can be quite large

31 4 However, the overall impact in the population can be quite large

32 4 However, the overall impact in the population can be quite large Risk ratio = 2.3 for each standard deviation of PM2.5

33 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%)

34 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%) 1.5% One SD below the mean 3.5% One SD above the mean

35 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%) 2% absolute difference in risk 1.5% One SD below the mean 3.5% One SD above the mean

36 4 However, the overall impact in the population can be quite large Births categorized by amount of prenatal exposure to air pollution (PM2.5)

37 4 However, the overall impact in the population can be quite large Risk ratio = 2.3 for each standard deviation of PM2.5 ASD prevalence 8.5% ASD prevalence 0.1% Births categorized by amount of prenatal exposure to air pollution (PM2.5)

38 4 However, the overall impact in the population can be quite large Births categorized by amount of prenatal exposure to air pollution (PM2.5)

39 4 However, the overall impact in the population can be quite large Births categorized by amount of prenatal exposure to air pollution (PM2.5)

40 4 However, the overall impact in the population can be quite large Population ASD prevalence down from 1.5% to 1.4% (3% reduction in ASD cases in the population overall) Births categorized by amount of prenatal exposure to air pollution (PM2.5)

41 4 However, the overall impact in the population can be quite large Births categorized by amount of prenatal exposure to air pollution (PM2.5)

42 4 However, the overall impact in the population can be quite large Births categorized by amount of prenatal exposure to air pollution (PM2.5)

43 4 However, the overall impact in the population can be quite large Population ASD prevalence down from 1.5% to 0.8% (47% reduction in ASD cases in the population) Births categorized by amount of prenatal exposure to air pollution (PM2.5)

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45 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

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48 QUESTIONS?