11. ASSOCIATION ANALYSIS

Question 1

Define genetic association

Answer 1

Genetic association is the idea that an allele occurs in a higher frequency than expected in unrelated individuals with the disease or trait compared to those without it
- The gene co-occurs with a phenotypic trait or disease

Question 2

What are case-control studies?

Answer 2

• Case-control studies compares the SNPs of individuals with trait to individuals without the trait
• Uses thousands of individuals
• Individuals must be well matched for risk factors such as age, sex, ethnicity etc.
• Definition of the disease or trait studied must be rigorously applied with a strict criteria

Question 3

What are the steps for a case-control study?

Answer 3

1. Affected & unaffecetd individuals are matched fro risk factors
2. Measure genetic loci of interest in both groups
3. Statistical analysis to determine which genetic loci are associated with disease
4. Identify genes

Question 4

What are the 7 requirements for an ideal genetic marker?

Answer 4

• A genetic marker are alleles that can be genotyped & can be assessed to see whether they’re associated with the disease
  1. Must be polymorphic (have at least two forms)
  2. Randomly distributed across the genome, so that it can end up near the disease gene due to chance
  3. Fixed location
  4. Frequent in the genome
  5. Frequent in the population
  6. Stable with time
  7. Easy to assay

Question 5

What’s the major & minor allele?

Answer 5

• SNPs are bi-allelic meaning that there are two possible alleles: a major & minor allele
• The major & minor allele should add up to 1
• The minor allele is the less common allele

Question 6

What MAF should SNPs have to be used in association studies?

Answer 6

• SNPs ideally should have a MAF of 0.05 (5%) to be used in association studies
• Exceptions aremonogenic SNPs

Question 7

What is a genome wide asociation study(GWAS)?

Answer 7

• A genome wide association study is an observational study that looks at the whole genome & sees if any variants are associated with a disease
• Uses a large number of controls & cases
• Genotypes genetic markers distributed across the genome, uses SNP microarrays

Question 8

How can the results from GWAS be plotted?

Answer 8

• ## GWAS can be plotted with a Manhattan plot where the position of the SNP will be on the x axis with the position of association on the y axis

Question 9

What do the peaks in Manhattan plots show?

Answer 9

A peak indicates a difference in the SNPs between the two groups

• However, SNPs are proxy markers they don’t identify the causative disease gene
• They can only identify the the region in which the gen is in, however this can be as large as 100kb

Question 10

What ahs GWAS showed about obesity?

Answer 10

• GWAS has shown that there are many loci associated with obesity or BMI-related traits