Common Complex Traits

Question 1

the chances of you getting the disease when you have the variant
(y side of disease traits graph)

Answer 1

variant effect size

• mendelian genes have high variant effect size meaning if you have the gene getting the trait is very likely

Question 2

the percentage of the population with a certain variant from rare to common
(x side of disease trait graph)

Answer 2

variant frequency

Question 3

The variants underlying genetic traits can vary in frequency and effect size …. variants have a high variant effect size and are rare

Answer 3

Mendelian

• simple mendelian : gene-> trait
• mendelian traits with modifiers: gene1 +gene2 -> trait or gene + env -> trait
• pleiotropic mendelian : gene -> trait 1, trait2, trait 3

Question 4

The variants underlying genetic traits can vary in frequency and effect size … variants are common but have very small effect sizes

Answer 4

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.

Question 5

The variants underlying genetic traits can vary in frequency and effect size … variants are rare and have a small variant effect size

Answer 5

rare, small effect variants

• very difficult to identify

Question 6

The variants underlying genetic traits can vary in frequency and effect size … variants that are common with large variant effect size

Answer 6

common, large effect variants

• not common in population

Question 7

what gene -> trait for mendelian with modifier?

Answer 7

gene + environment -> trait

OR

gene + gene -> trait

Question 8

what gene -> trait for pleiotrophic mendelian?

Answer 8

gene -> trait 1, trait 2, trait 3

Question 9

what gene -> trait for complex mendialian ?

Answer 9

genes + environment -> trait

Question 10

what relationships should you look at to the heritability of a trait?

Answer 10

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

Question 11

this is the amount of phenotypic variation in a population that is due to genotypic variation

Answer 11

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

Question 12

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).

Answer 12

population
genetics

• the higher the heritability, the higher the correlation bt individuals (ex: height) trait and the mean of their parents (height) traits

Question 13

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

Answer 13

Genome wide association studies (GWAS)

Question 14

steps of GWAS

Answer 14

looks at unaffected vs affected cohort for condition of interest

1. genotype individuals for SNPs across genome - uses microarray that looks for sequence changes
2. map out allele frequencies of SNPs for both cohorts (Manhattan plot of SNPs)
3. are any of the variants associated with disease? Find out by calculating Odds ratio
   * odds of being affected
4. 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

Question 15

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

Answer 15

missing heritability

Question 16

missing heritability is a measure of the amount of … caused by genetics that is not attributable to known ..

Answer 16

phenotypic variation

known variants

Question 17

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 ..

Answer 17

genetics

Question 18

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

Answer 18

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