Week 10 - Complex Traits

Question 1

How does a case control GWAS work?

Answer 1

• Genome-Wide Association Studies
• two comparable groups e.g. same racial group
• one is affected cases
• other is unaffected controls
• gentic loci of interest is measured
• statistical analysis is used to determine which genetic loci is associated with the disease

Question 2

What is linkage disequilibrium?

Answer 2

• also called allelic association
• when alleles at 2+ loci are found together in a population more frequently than would be expected by chance
• tag SNP is analysed to learn about its inheritance

Question 3

What is haplotype?

Answer 3

• genetic variants inherited together from one parent
• differs from LD as that is from a population

Question 4

What does a Manhattan plot show?

Answer 4

• each dot represents statistical analysis of one SNP
• to identify LD and haplotype blocks

Question 5

What are the advantages and disadvantages of GWAS?

Answer 5

• advantages
• no prior knowledge of genomic intervals associated with the disease required
• no family or pedigree information
• identify many genomic intervals associated with a disease
• disadvantages
• expensive
• complex statistics
• hard to replicate findings
• assumes that common disease is caused by common variants

Question 6

What is the polygenic model of inheritance?

Answer 6

• continuous traits are determined by mani loci
• loci are additive
• only considers genes

Question 7

What is a liability model?

Answer 7

• considers genes and environment
• continuous trait
• threshold creates dichotomous state
• beyond threshold would be affected individuals
• threshold shifts when there is familial incidence of disease
• due to more liability factors

Question 8

What is heritability?

Answer 8

• proportion of phenotypic variation directly due to genetic differences between individuals in a population

Question 9

How is heritability estimated?

Answer 9

• monozygotic twins
• same genes and environment
• dizygotic twins
• 50% same genes
• same environment
  OR
• within families
• phenotypic variation
• correlated with expected degrees of similiarity between relatives
• e.g. parents and children = 1^st degree = 1/2
• grandchildren = 2^nd degree

Question 10

What is concordance?

Answer 10

• twins having the same phenotype
• different phenotype = discordance
• MZ concordance rate is higher means greater genetic contribution
• MZ concordance rate is similar to DZ means greater environmental contribution

Question 11

What is sib risk?

Answer 11

• risk of siblings of an affected person developing trait of interest
• compared to general population
• incidence in group of siblings divided by population incidence