the chances of you getting the disease when you have the variant
(y side of disease traits graph)
variant effect size
- mendelian genes have high variant effect size meaning if you have the gene getting the trait is very likely
the percentage of the population with a certain variant from rare to common
(x side of disease trait graph)
variant frequency
The variants underlying genetic traits can vary in frequency and effect size …. variants have a high variant effect size and are rare
Mendelian
- simple mendelian : gene-> trait
- mendelian traits with modifiers: gene1 +gene2 -> trait or gene + env -> trait
- pleiotropic mendelian : gene -> trait 1, trait2, trait 3
The variants underlying genetic traits can vary in frequency and effect size … variants are common but have very small effect sizes
common complex
- could be multiple genes + env to -> trait
- many diff env + genetic factors
ex: type 1,2 diabetes, height, high cholesterd, CHD, depression etc.
The variants underlying genetic traits can vary in frequency and effect size … variants are rare and have a small variant effect size
rare, small effect variants
- very difficult to identify
The variants underlying genetic traits can vary in frequency and effect size … variants that are common with large variant effect size
common, large effect variants
- not common in population
what gene -> trait for mendelian with modifier?
gene + environment -> trait
OR
gene + gene -> trait
what gene -> trait for pleiotrophic mendelian?
gene -> trait 1, trait 2, trait 3
what gene -> trait for complex mendialian ?
genes + environment -> trait
what relationships should you look at to the heritability of a trait?
parent/child correlation
sibling risk
twin studies
- Comparing a trait in parents and children, siblings, and twins can indicate if it has a genetic basis
this is the amount of phenotypic variation in a population that is due to genotypic variation
heritability
- in a complex trait heritability could help you understand genetic basis of a trait at population level only not individual
- heritability is a population- specific metric
can differ between populations
A trait is determined to be 60% heritable This means that 60% of the variability of the trait in the (population/individual) is due to (genetics/environment).
population
genetics
- the higher the heritability, the higher the correlation bt individuals (ex: height) trait and the mean of their parents (height) traits
these allow for the investigation of the variants the underlie complex traits
used to identify regions of the genome with a statistically significant association with a particular trait
Genome wide association studies (GWAS)
steps of GWAS
looks at unaffected vs affected cohort for condition of interest
- genotype individuals for SNPs across genome - uses microarray that looks for sequence changes
- map out allele frequencies of SNPs for both cohorts (Manhattan plot of SNPs)
- are any of the variants associated with disease? Find out by calculating Odds ratio
* odds of being affected - apply statistical tests to see variants seen in affected vs unaffected are significant
*Different affected individuals generally have different risk variants, so no single variant is likely to be found in all affected individuals. Therefore, you cannot expect to see a complete correlation between the presence of a variant and presence of a condition, but instead need to look for enrichment of a variant in the affected population, compared to the unaffected
this is is the amount of heritability of a trait that cannot be accounted for by variants currently known to contribute to that trait
*may be due to unidentified rare variants, weak effect variants, genetic and environmental interactions
missing heritability
missing heritability is a measure of the amount of … caused by genetics that is not attributable to known ..
phenotypic variation
known variants
each complex trait has a different amount of heritability which tells us how much of a variation in that trait could be accounted for by ..
genetics
General population risk for complex traits is different than individual risk depending on social determinants of the individual.
Complex trait risk is determined by cumulative effects of many .. .. .. and the environment
small effect variants (combination of genetic factors)
- complex trait Risk of an individual can be estimated from risk of a subset of individuals who have similar characteristics
- Risk can be reported as absolute or relative risk, and in the case of the latter, it is important to know the baseline risk
