Psychopathology: Week 3

Effects of loci

Large number of contributing loci, each locus effects is small and approximately equal, effects add up over loci

Biometric tradition

Can estimate genetic and environmental effects even when individual loci, genes, environments are unknown

How is the diathesis/gene- stress/environment modeled mathematically?

Biometrical decomposition

What’s the biometrical decomposition equation? 

P = G + E (GxE)

P= phenotype

G= genes

E= environemnt

GxE= gene-environment interaction

Usually simplified as P= G + E

What are the expanded terms of rthe biometrical decomposition equation?

P= (A + D + I) + (CE + NE + ME)

A: Additive genetic effects

D: Dominance genetic effects

I: Epistasis genetic effects

CE: Shared environment

NE: nonshared environment

ME: measurement error

What is the additive genetic effect?

A: effects of alleles taken singly aggregated across loci

What do shared environements mean in the biometrical decomposition? 

CE: environemtn that contributes to sibling similarities 

What do non-shared environments mean in the biometrical decomposition?

NE: environment that contributes to sibling differences

Measurement error in the biometrical decomposition equation

ME: errors in measuring the phenotype as well as short-term temporal instability

What does “e” mean in the biometrical decomposition equation? 

It is the non-shared environment and the measurement error added together 

Phenotypic variance model (original, expanded, and simplified to equal 1)

Original:

V_P= V_G + V_E

Variance of G is how different genes are, variance of E is how different enviornments are

Expanded:

V_P= V_A + V_CE + V_NE +V_ME

Adds up to 1:

1= a² + c² + e²

a²=heritability

c²= shared environment

e²= non-shared environment

What is heritability?

It is:

• The proportion of phenotypic variance that is attributable to genetic variance in the sample

• an index of the extent to which genetic factors currently predict phenotypic differences in the sample of individuals under study

It is not:

• an index of whether a phenotype is genetically fixed or determined

Hans Eusenck and Arthur Goldberer on heritability 

Eusenck: social policies aren’t necessary if things are genetically determined (such as an individual’s earning capacity)

Goldberger: Just because things are heritable don’t mean you shouldn’t do anything about it (ex: eyeglasses)

What are examples of heritable traits?

Height is highly heritable

• not fixed though, also impacted by nutrition, medicine, etc.

Reading ability

• a² effect is high and c² effect is low when receiving the same reading instruction

What is the equation for familial resemblance for a quantitative phenotype?

cor(P1, P2) = r_aa² + r_cc²

r_a= probability that 2 relatives share a randomly selected allele at a randomly selected locus identical by descent 

r_a=(1/2)ⁿ

n= degree of relationship (1st degree, 2nd degree) 

r_c= usually specified as 1 for reared-together relative and 0 otherwise (this is open to interpretation) 

What are the familial resemblances for quantitative phenotypes based on degrees of relationship?

MZ twins reared together, apart, DZ twins, Parent-offspring, half siblings

What is the principal of additivity?

There are 5 sources of variance (a², d², i², c², e²) but only 3 are usually used in practice (a², c², e²) to approximate the major sources of phenotypic variance

Can a precise determination of heritability (a) be found? Why or why not? 

What about c and e? 

Approximate estimates of heritability can be found, but not precise determinations, this is because: 

• heritability is not a fixed constant

• assumtion are needed to calculate heritability 

  • Additivity of genetic effects

  • Nature of environmental transmission

  • No GxE interaction

  • No G-E correlation

The same issues can apply to c and e