Interplay between Genes and Environment

1. Interplay between Genes and Environment

2. 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

3. 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….

4. Environment • Gosh, it’s 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…

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

6. Genotype-Environment Correlation • People create their own experiences, partially for genetic reasons • “Nature of nurture”

7. Genotype-Environment Interaction • Effect of environment can depend on genetics… • And, effects of genetics can depend on the environment. • Genetic sensitivity to environments

8. 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

9. Testing for Shared Environment • Direct test • Resemblance among adoptive relatives • Zero heredity

10. 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 don’t • Need to account for this when calculating nonshared effect

11. 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

12. 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 didn’t account for a lot of the variability

13. However… • Plomin, Ashbury & Dunn (2001) • Each factor doesn’t, 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

14. 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

15. 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

16. 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

17. 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”

18. 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

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

20. 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 • Can’t give full picture of gene to behaviour pathway • Must consider the extended phenotype pathways • Standard heritability estimates can’t distinguish between inside and outside the skin pathways • Needs to be addressed given non-trivial role of genotype-environment correlation

21. 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

22. Method 1 • Only usable to detect passive • See if genetically influenced parental traits correlate with both the environmental measure and the children’s trait • Compare correlations in biological and adoptive families • Adoptive parents genetically different from adopted children • If correlation greater in biological family, there’s a passive genotype-environmental effect

23. 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 children’s genetic propensities (partially shared with the biological parents)

24. 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

25. 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

26. Genotype-Environment Interaction • Genotype-environment correlation: role of genetics in exposing an individual to environmental factors • Genotype-environment interaction: individual’s susceptibility to specific environments due to genotype • Effect of environment on phenotype depends on genotype, or • Effect of genotype on phenotype depends on environment

27. 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

28. 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 • Can’t manipulate environment experimentally, but can take advantage of changed environment via adoption • Twin studies • Can use one twin’s phenotype as index of co-twin’s genetic risk for some trait • Typically determining if heritability differs in two environments

29. 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…

30. 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.