Other studies to ACE Flashcards
Family studies
Sibling/cousin/second cousin… cacluate the relative risk - how much more likely are you to get a disease if your sibling/cousin/second cousin has it
Familial risk - how much does a family history of a disease increase your risk
This assumes that all similarity in a family is due only to genetics - i.e. that there is no “common environment
Adoption studies
Correlation between MZ twins that have been adopted and raised separately
Precisely estimates H2 (i.e. accounts for dominance/interactions etc)
Very hard to get enough twin pairs to make a good estimate
Twins might not be assigned to a random environment - might be adopted by people who can give an “approved” upbringing.
None specialist often assume this is how heritability is usually measured
Mixed linear models
Complex statistical models that can make use of similarities in complex pedigrees
Can use data from people with a mixture of different relationships
Can use genotyping data to calculate precise genetic similarity
Computationally challenging
Prone to something called “model selection bias”
Odds ratio describe
Effect of a single gene
Where do we think heritability comes from?
Large number of genes with small effect
What is an individuals genotype composed of?
More than just one varient
It is combined effect of the alleles at 15 million different locations
What can we see with an individual with more risk alleles
will be a higher risk of disease
Polygenic risk score
Combination of
- more risk alleles, higher risk of disease
- carrying risk alleles with bigger effect sizes wi.l have a higher genetic risk than those carrying lower effect size risk alleles.
To calculate score: go through each SNP associated with a trait of disease and multiply the odds ratio for that gene by the number of risk alleles that that individual has for that site.
Then add this up for all variants to get final score. Those with higher score have a higher genetic propensity to the disease or trait.
What do GWAS studies address?
Additive/ narrow-sense heritability
WHat do twin studies measure?
closer to braod sense heritability - but not quite
WHats the idea of narrow-sense heritability or additive variation?
That each additional alles shifts your phenotype by the same amount - so homozygous locus has twice the effect of a heterozygous SNPs.
Where might deviate from narrow-sense heritability or additive variation?
Dominance, epistasis and gene by environment interactions
Gene-by environment interaction
Gene–environment interactions are the situation where the impact of an environmental exposure on disease risk is different for people with different genotypes, or conversely, situations where the impact of a genotype on disease risk is different in people with different environmental exposures.
Dominance variation
Alleles at the same locus affect eachother, so that the effect of a homozygous is not twice the effect of a heterozygote.
For example, on classic dominance, being heterozygous might have no effect, while being homozygous has a big effect. Two copies of the allele are said to interact with eachother.
Epistasis
Alleles at two different loci interact with eachother.
Under epistasis, might get no effect of minor alleles at locus 1 if locus 2 it WT. 10 for each locus 1 alleles for a locus 2 heterozygote. 20 for each locus 1 allele for a locus 2 heterozygous minor allele.
