Genetic vs. Environmental Hypotheses of Disease Causation:

1
Genetic vs. Environmental Hypotheses of Disease
Causation The Case of Autism
Holly K. Tabor, Martine Lappé, Marci Pepper, Mona
Mohindra, Angie Boyce and Mildred Cho Stanford
Center for Biomedical Ethics, Stanford
University, Palo Alto, CA 94304-5748

• Framing of Genetics
• Presenters framed the role of genetics in the
  causation of autism in three main ways.
• 1) Genetics Does Not Play a Role, Only
  Environment
• Autism cant be caused by genetic factors because
  its an epidemic, and epidemics cant be genetic.
• There is no genetic disorder that increases from
  one in 10,000 to one in 160 in one generation.
  There has to be some sort of environmental
  trigger.
• -Clinician
• 2) Gene-Environment Interaction
• Genetic factors increase risk of autism by
  creating a genetic susceptibility, inhibiting
  the ability of people to process toxins that they
  are exposed to in the environment.
• This would be a specific mercury vulnerability
  factor. It is not an autism gene, in the sense
  that it doesnt build an autistic brain, but it
  makes you vulnerable to the potential effects of
  mercury, and it makes you likely to have
  autoimmune disease . . .
• -Clinician
• 3) Epigenetics as a Model for Gene-Environment
  Interaction
• Autism is caused by inherited or somatic
  epigenetic changes.

• Analogous Disease Comparisons
• Presenters used several disease analogies to help
  model their understanding of causation, and the
  role of genetics in causation.
• Genetic Disease of Toxin Metabolism
• Wilsons Disease an inherited metabolic disease
  caused by a mutation in the ATP7B gene, coding
  for a copper transport protein
• Results in the accumulation of copper in tissues
• Wilson's disease is one of the rare treatable
  genetic disorders. Not very many genetic
  disorders can be treated. -Toxicologist
• 2) Genetic Diseases with Autism-Like Symptoms
• Rett Syndrome, Fragile X
• 3) Diseases Caused by Environmental Exposure with
  Developmental Symptoms
• Micromercurialism
• 4) Diseases Requiring a Paradigm Shift in
  Methodology
• Neural Tube Defects
• I would implore the committee to consider . . .
  the best way to study this is to study it with
  populations at risk. That is how we found folic
  acid and neural tube defects. If you looked at
  folic acid and neural tube defects and did this
  epidemiology, you might not see it . . . it may
  not be that 100 percent of children with autism
  have this, so you would miss it if there is a
  subset of children that have it.

Complex diseases have both genetic and
environmental components, and the genetic
component may be due to a large number of genes
of small effect size. The proliferation of
studies on the genetics of complex traits has
resulted in conflict around what it means if a
disease is primarily environmental or genetic in
origin. We analyzed a public debate about the
causation of one complex disease autism. Autism
is a neurodevelopmental disorder with markedly
abnormal social interaction, communication
ability, patterns of interests, and patterns of
behavior. Autism is thought to have a strong
genetic component, yet no single-genes have been
conclusively identified that account for most of
the cases. In the last ten years there has been
significant public debate about the role of
vaccines in causing autism, specifically vaccines
containing thimerosal, a mercury-based
preservative, and the Measles Mumps Rubella (MMR)
vaccine. In 2004 the Institute of Medicine
(IOM) convened a panel to examine the possible
role of vaccines containing the mercury
preservative thimerosal and MMR vaccines in
causing autism. Scientists from a range of
disciplines and perspectives were invited to
present data in public testimony. This session
was a unique snapshot of public scientific
discourse on causation expert scientists
speaking to scientist panel members in a public
forum. We analyzed the transcripts of the
speakers using a qualitative textual analysis
software (MaxQDA). The goal was not to evaluate
the accuracy or strength of the evidence
presented or the quality of the science on which
it was based. The goal was to characterize the
language used to frame the roles of genetics and
environment in causation. The data set included
thirteen presentations, each lasting 20 minutes
with 10 minutes of question and answer time. Six
presenters came from academic institutions, five
from government agencies and two from private
research organizations. Five of the presenters
were epidemiologists. The remainder included a
toxicologist, a neurosurgeon, a clinician, an
immunologist, a chemist, a microbiologist, a
pharmacologist and a geneticist.
Research supported by NHGRI and DOE