Association analysis

Question 1

What is genetic association?

Answer 1

Genetic association is the presence of a variant allele at a higher frequency in unreliable subjects with a particular disease, compared to those that do not have the disease

Question 2

What is an allele?

Answer 2

One form of a varient in the genome

Question 3

What is a locus?

Answer 3

A position in the genome

Question 4

What is a genotype?

Answer 4

Both alleles at a locus

Question 5

What is a haplotype?

Answer 5

It is the order of alleles along a chromosome

Question 6

What are cases?

Answer 6

Cases are subjects with the disease of interest

Question 7

What do case control association search for?

Answer 7

Search for variant in cases and control

Refer to diagram in notes as well or PPT to those using my flashcards

Question 8

What do the best case control genetic studies have?

Answer 8

Have:

• Large number of well designed cases
• Equal numbers of matched controls
• Reliable genotyping technology(SNP array)
• Standard statistical analysis(PLINK)
• Positive results must be replicated

Question 9

What are ideal characteristics of genetic markers?

Answer 9

• Polymorphic
• Randomly distributed across the genome
• Fixed location in genome
• Frequent in genome
• Frequent in population
• Stable with time
• Easy to assay

Question 10

What is dbSNPs?

Answer 10

Database of SNPs

Question 11

What are on the either sides of SNPs?

Answer 11

There’re unique flanking sequences on either side of the SNP

Question 12

What is the rs number?

Answer 12

The rs number is a unique identifier given to each SNP

Question 13

What is the less common allele referred to as?

Answer 13

Referred to as the minor allele

Question 14

What do GWAS use and give an example?

Answer 14

Use markers across the whole genome

Question 15

What are we usually looking for in GWAS and what test can we use to statistically confirm a link?

Answer 15

Looking for an association between the disease and each marker
-Chi-squared test

Question 16

In what way is GWAS data presented as?

Answer 16

Presented as a single graph called a manhattan plot

Question 17

What do the x and y axis in a GWAS results plot represent?

Answer 17

x axis- Position of the SNP on the chromosome

y axis- (-log(P-value)) of the association

Question 18

In GWAS results, what does the peak identify and not identify?

Answer 18

Identifies genomic region associated with the disease

Does not identify the gene causing the disease

Question 19

What does meta analysis allow and why is it easier?

Answer 19

Allows the statistical combination of results from multiple studies

-Easier to combine smaller studies than having to do large studies

Question 20

What are the problems with GWAS?

Answer 20

• GWAS has identified associations that are statistically strong and reproductive
  - However contribution to the genetic component of disease is estimated to be low due to:
  - Epigenetic variation
  - Heritability is overestimated
  - Common SNPs of small effect
  - Rare SNPs
  - Copy number variation