Interplay between Genes and Environment

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Interplay between Genes and Environment
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Gene Expression

• Evolved to be responsive to intracellular and
  extracellular environments
• Biological index of environmental influence
• Phenotype model
• Assess environmental influence by its change in
  gene expression profiles across genome

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Caveats

• Know a lot more about genes than environment
• E.g., from base pairs, on chromosomes,
  transcription, etc.
• Questions
• Where are environmental effects expressed in
  brain?
• How do environmental effects change with
  development?
• How does environment cause individual differences
  in behaviour?
• Etc., etc., etc.

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Environment

• Gosh, its important
• Demonstration through quantitative genetics
• Heritability rarely more than 50
• Hence, environmental effects typically going to
  account for over 50 of individual differences
• Three rather important discoveries

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Nonshared Environment

• Environmental influences make children in same
  family no more similar than children in other
  families
• Rather a surprise for traditional psychology
  theories

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Genotype-Environment Correlation

• People create their own experiences, partially
  for genetic reasons
• Nature of nurture

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Genotype-Environment Interaction

• Effect of environment can depend on genetics
• And, effects of genetics can depend on the
  environment.
• Genetic sensitivity to environments

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Environment

• Shared environment
• Family resemblance not explained by genetics
• Nonshared (unique) environment
• Variance not explained by heredity or shared
  environment
• Includes error of measurement
• Note shared nonshared not limited to family
  environments
• Experience outside family can be shared or
  nonshared by siblings

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Testing for Shared Environment

• Direct test
• Resemblance among adoptive relatives
• Zero heredity

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Testing for Nonshared Environment

• Direct test
• Identical twins
• Same genetics
• Generally share same environment
• So, difference due to nonshared
• But, a conservative estimate
• Twins often share special environments that
  non-twin sibs dont
• Need to account for this when calculating
  nonshared effect

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Specific Nonshared Environment

• Assess elements of environment specific to each
  child
• Not aspects shared by all siblings
• What specific factors make children in same
  family so different?
• Remember factors specific to a child can also be
  shared by other child(ren) in family too

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Factor and Behaviour

• So you identify a child-specific factor. Does it
  actually relate to behaviour?
• E.g., do a difference in parental treatment
  really make a kid schizophrenic?
• Turkheimer Waldron (2000)
• Overall, specific non-shared environment factors
  didnt account for a lot of the variability

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However

• Plomin, Ashbury Dunn (2001)
• Each factor doesnt, but add the specific factors
  up and you start to get somewhere

Factor Variance accounted for
in adjustment, personality, cognitive Birth
order 0.01 Differential parental
behaviour 0.02 Differential sib
interactions 0.02 Differential peer or
teacher interactions 0.05 Several other
factors 0.03 Total 0.13
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Direction

• Remember correlation is not causation
• Does parent treatment cause the behaviour, or
  does the behaviour cause the parental treatment?
• Starting to look like the genetics of a child can
  have a role on the behaviour of the parent
• Child appearance
• Berkowitz Frodi (1979) unrelated adults
  punished unattractive children more than
  attractive children
• Allen et al. (1990) mothers less verbal and more
  controlling of their children with congenital
  facial anomalies

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Other Issues

• Chance
• Random events are another factor contributing to
  nonshared environment
• Age differences
• Specific factors in nonshared environment are
  going to change markedly across development

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So

• Environmental influences do affect behaviour
• More individual-by-individual than
  family-by-family
• Family experiences are important, but these
  environmental events will affect different
  individuals in different ways

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Genotype-Environment Correlation

• Genotype can influence environmental factors
  effects
• Individuals have an active role in selecting,
  modifying, and constructing their environment
• Extended phenotype
• Niche construction

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Kendler Baker (2007)

• 55 independent studies that estimated genetic
  influences on an environmental variable
• Seven categories
• General and specific stressful life events,
  parenting as reported by child, parenting as
  reported by parent, family environment, social
  support, peer interactions, and marital quality
• 35 environmental measures from these categories

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Results

• Weighted heritability estimates from 7-39 for
  individual environmental measures
• Most between 15-35
• Weighted heritability for all environmental
  measures was 27
• An individuals genetic influences on his/her
  environment account for 25 of the variance in
  the nonshared environment component of behaviour

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Implications

• Strongly support the bi-directional model of
  person environment inter-relationships
• Humans actively create important aspects of their
  social environment and interpersonal
  relationships
• Molecular genetics advances promote
  reductionistic models of inside the skin gene
  effects
• Cant give full picture of gene to behaviour
  pathway
• Must consider the extended phenotype pathways
• Standard heritability estimates cant distinguish
  between inside and outside the skin pathways
• Needs to be addressed given non-trivial role of
  genotype-environment correlation

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Three Types of Genotype-Environment Correlations

• Passive
• Children passively inherit family environments
  from their parents that are correlated with their
  genotype
• Interactions between genetically related
  individuals
• Evocative (aka reactive)
• Individuals, due to genotype, evoke reactions
  from other people
• Between anyone who reacts to individuals due to
  their genetic proclivities
• Active
• When individuals select, modify, etc. experiences
  that are correlated with their genetic
  propensities
• Between anyone or anything in the environment

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Method 1

• Only usable to detect passive
• See if genetically influenced parental traits
  correlate with both the environmental measure and
  the childrens trait
• Compare correlations in biological and adoptive
  families
• Adoptive parents genetically different from
  adopted children
• If correlation greater in biological family,
  theres a passive genotype-environmental effect

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Method 2

• For evocative and active
• Compare biological parents traits and adoptive
  families environments
• Biological parents share genes with adopted away
  children adoptive parents react to the adopted
  childrens genetic propensities (partially shared
  with the biological parents)

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Method 3

• Can be used on all three types
• Multivariate genetic analysis of correlation
  between an environmental measure and a trait
• Estimates degree to which genetic effects on one
  environmental measure overlap with other genetic
  effects on a second measure

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In a Nutshell

• Passive seems most important in childhood
• Evocative and, especially, active increase in
  significance with development
• With age, individual does more to direct his or
  her own environmental interactions, in part
  driven by own unique genotype

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Genotype-Environment Interaction

• Genotype-environment correlation role of
  genetics in exposing an individual to
  environmental factors
• Genotype-environment interaction individuals
  susceptibility to specific environments due to
  genotype
• Effect of environment on phenotype depends on
  genotype, or
• Effect of genotype on phenotype depends on
  environment

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Possibilities

• G has effect without effect of E
• E has effect without G
• Both G and E have an effect
• Both G and E have an effect and interact with
  each other

QT
QT
Low risk High risk G G
Low risk High risk G G
QT
QT
Low risk High risk G G
Low risk High risk G G
QT phenotypic quantitative trait
High risk E
G genetic effects
E environmental effects
Low risk E
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Study Designs for Testing G-E Interaction

• Non-human animal studies
• Have the advantage of being able to manipulate
  and control both genotype and environment
• Adoption studies
• Cant manipulate environment experimentally, but
  can take advantage of changed environment via
  adoption
• Twin studies
• Can use one twins phenotype as index of
  co-twins genetic risk for some trait
• Typically determining if heritability differs in
  two environments

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General Findings

• Non-human animal models tend to show
  interactions, but not consistent
• E.g., maze-bright maze-dull in enriched vs.
  restricted environments
• Problem for animal models is that there is
  limited opportunity for a rat in a cage to extend
  his phenotype

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• Some adoption studies support, but others fail to
  find, genotype-environment interactions
• Twin studies generally find some effect
• Not a lot of molecular genetic QTL work on this
  yet, but what there is shows effects
• E.g., COMT allele and cannabis use study
• Overall, support for modest genotype-environment
  interaction
• A lot of variability in results depending on what
  environmental measure is being used
• E.g., cognitive, psychopathology, attitude,
  personality, etc.