D. GWAS

Question 1

How to examine statistical association between genotypes and phenotypes?:

Answer 1

1. A comparison is always made between two groups of samples. 2. The two groups are divided
2. Study design 1 or 2 compares between two groups
3. statistics test whether the two groups are significantly different or not.

Question 2

What data is compared between 2 groups in GWAS designs?

Answer 2

D1: variant frequency — Increased frequency per variant/locus is analyzed throughout the entire genome.
D2 : average phenotype —Association is analyzed by comparing phenotypic means (distribution) between the two groups. Significantly different mean phenotype indicates an association.

Question 3

How are individuals divided between 2 groups in GWAS designs?

Answer 3

D1: divided into categorical variants: unaffected and affected.
D2: divided into two phenotypic classes by genotype

Question 4

In a diploid organism like a human, the two groups are divided by two distinct ways according to two inheritance models, recessive or dominant. At a given variant B,

Answer 4

The dominant model: all individuals with B/B or B/non-B genotype will be affected by B. The recessive model: only the individuals with B/B will be affected by B.

Question 5

What do GWAS examine?

Answer 5

At a given population, GWAS examines statistical association between the genotype and phenotype in all possible examinable variant locations or loci.

Question 6

An important note is that the identified variants in multi- genic phenotype study never reach to 100% frequency in the affected individuals,

Answer 6

Mendelian disease study depends on the variant frequency 100% in the affected individuals.

Question 7

Why have we done so many GWAS studies before?

Answer 7

GWAS still discovers ‘associated variants’ to a phenotype (ex. cancer or diabetes) among the common variants.