Association Analysis

Question 1

What is genetic association?

Answer 1

Genetic association is the presence of a variant allele at a higher frequency in unrelated subjects with a particular disease (cases), compared to those that do not have the disease (controls).

For disease, we could use the broader term ‘trait’, for example, height is not a disease.

Question 2

What are case control studies?

Answer 2

Cases: subjects with the disease of interest

The controls must be as well-matched as possible for non-disease traits (sex, age, ethnicity, location, etc). Thus, they must be identical to the cases but just not have the disease.

Question 3

How would case control studies be used for genetic association?

Answer 3

1. You would match the affected cases and unaffected controls for all the other risk factors.
2. You would measure the genetic loci of interest.
3. You would perform a statistical analysis to determine which genetic loci correlate with each disease.
4. You would identify the genomic region associated with the disease.

Question 4

What are some features of an ideal case control study?

Answer 4

• large numbers of well-defined cases (1000s)
• equal numbers of matched controls
• reliable genotyping technology (SNPs are used)
• standard statistical analysis (PLINK is used)
• positive associations should be replicated

Question 5

Why do we need genetic markers?

Answer 5

Individuals in a population are genetically far more diverse than individuals in a single family.

To capture this genetic diversity, we need to use 100s