Transcript Gene-environment correlation

Gene-environment interaction
and
Gene-environment correlation
Charlotte Huppertz
VU University Medical Center Amsterdam
Netherlands Twin Register
Book recommendation
Chapter: “The interplay between genes and environment”
 References to
studies that will be
mentioned
Background
• Assumption: no GxE interaction or correlation
• However: genes and the environment are not two
separate entities
• They can interact and they can be correlated
• This may influence the phenotypic variance
GENE-ENVIRONMENT INTERACTION
Gene-environment interaction
Definition
• The effects of the environment can depend on
genetics, and the effects of genetics can depend on
the environment
• Genes evolved to respond to the environment
• Environment = all influences other than inheritance,
including intracellular and extracellular factors
Pima Indians in Arizona
• Followed since 1965
• Highest reported prevalence of type 2 diabetes
• Traditional agricultural goods  processed foods
Effects on estimates
If G-E interaction is not modelled, it will bias the estimated parameters
Effects on twin resemblance:
A
C
AxC
MZ pairs
1
1
1x1= 1
DZ pairs
0.5
1
0.5x1= 0.5
An interaction with C would end up in the A-component, if not modelled.
A
E
AxE
MZ pairs
1
0
1x0= 0
DZ pairs
0.5
0
0.5x0= 0
An interaction with E would end up in the E-component, if not modelled.
Effects on estimates
• Hidden G-C interaction may be one of the reasons
why we rarely see C: The effects of the shared
environment may be modified by genes
• We should at least discuss this possibility
• Still, our results are meaningful – given a certain
environment
Gene-environment interaction
How to identify interaction?
• Animal studies
– Both genotype and the environment can be manipulated
– E.g. inbreeding
• Adoption studies
• Twin studies
• Molecular genetic studies
Gene-environment interaction
How to identify interaction?
• Animal studies
– Both genotype and the environment can be manipulated
– E.g. inbreeding
• A) Adoption studies
• B) Twin studies
• C) Molecular genetic studies
Gene-environment interaction
A) Adoption studies
• Adoptee
• Biological parents (shared genes)
• Adoptive parents (shared environment)
EXAMPLE: criminal convictions (CC)
CC adoptive parents
+ CC biological parents
→ CC child
CC adoptive parents
+ No CC biological parents
→ Less so...
Gene-environment interaction
B) Twin studies
„Does h² differ in two environments?“
EXAMPLE:
More permissive environment
 larger h² of alcohol use and abuse
 Environment needs to be the same for both twins
 Very large samples needed (e.g., 1000 pairs of each
zygosity to identify a difference in h² of 40% vs. 60%)
Gene-environment interaction
C) Molecular genetic studies
„Does the effect of specific genes differ in two environments?“
EXAMPLES:
• MAOA gene  antisocial behavior,
given childhood maltreatment
• 5-HTT gene  depression,
given stressful life events
• Cannabis use  psychotic symptoms (hallucinations …),
given a particular allele of the COMT gene
GENE-ENVIRONMENT CORRELATION
Gene-environment correlation
Many measures of the „environment“ show
genetic influence (~30%)
● SES
● Exposure to accidents
● Family environment
● Divorce
● Work environment
● Other life events
● Classroom environment ● Subjective processes
● Stress
● Friends
● Social support
in filling
out a
 Life involved
events and
circumstances
not „just
happen“ to us!
questionnaire
Genes & experiences are correlated.
…
Gene-environment correlation
Implication
• If an environmental measure is correlated with a
behavior, this doesn‘t automatically imply
environmental causation – it could also reflect
underlying genetic factors
• Parents affect children through their genes and
through the family environment – often difficult to
disentangle!
EXAMPLE: books & reading ability
Gene-environment correlation
3 types of correlations
• PASSIVE
– Children receive genotypes correlated with their family
environment
– Requires interactions between genetically related individuals
• REACTIVE/EVOCATIVE
– Individuals are reacted to on the basis of their genetic
propensities
• ACTIVE
– Individuals seek or create environments correlated with
their genetic propensities
Gene-environment correlation
How to identify correlation?
• 1) Compare adoptive vs. nonadoptive families
– Detects the passive type
• 2) Adopted children and their parents
– Detects the reactive and the active type
• 3) Multivariate genetic models
– Detects all types
Gene-environment correlation
1) Compare adoptive vs. nonadoptive families
• Factor in family environment  child‘s behavior
• Measure this factor and children‘s behavior both in
nonadoptive families and adoptive families
• Crucial difference:
– Adoptive families: parents pass on E
– Nonadoptive families: parents pass on A and E
• GE correlation is implied if the correlation is larger in
nonadoptive families
Gene-environment correlation
2) Adopted children and their parents
• Requires:
– adopted children
– their adoptive parents
– their biological parents
• Traits of biological parents = (weak) index of children‘s
genotypes
• Correlation of adoptive family environment with traits of
biological parents  environment & genetically
influenced characteristics of the adopted children are
correlated
Gene-environment correlation
3) Multivariate genetic models
Calculate the genetic correlation (overlap) between the
environmental measure and the trait
 the environmental measure must be specific to each
individual (e.g., family SES is not possible)
QUESTION: How would you estimate this overlap?
Take home messages
• Genes and the environment are not two separate
entities
• The effects of genes can depend on the environment
and vice versa (INTERACTION)
• Many environmental measures show genetic
influence (CORRELATION)