Polygenic Disease

Question 1

population stratification / confounding by ancestry

Answer 1

Question 2

Correcting for population stratification

Answer 2

Statistical methods are now built into GWAS algorithms to determine relatedness, which corrects for linked phenotype affects.

Question 3

Sample sizes for GWAS controls need to be. . .

Answer 3

at least in the thousands as a minimum

Question 4

Linkage disequilibrium enabled imputation

Answer 4

You may infer (or impute) genotypes you have not actually checked if you know what is associated with the individual’s haplotype.

Question 5

As a consequence of linkage disequilibrium, not all ___ need to be ___.

Answer 5

As a consequence of linkage disequilibrium, not all variants need to be genotyped.

Question 6

Sulfonylureas

Answer 6

Bind to and inhibit KCNJ11 (a potassium transporter ATPase) on pancreatic beta islet cells and induce depolarization, leading to calcium mobilization and downstream insulin release.

Major class of drugs used to treat a subset of Type II diabetes that is caused by insufficient insulin secretion due to mutations in ion channels and ion channel regulators.

Question 7

Manhattan Plot

Answer 7

Each dot is a variant, the X-axis is the position in the genome and the Y-axis is the strength of association; if you look closely you can see a dashed line that corresponds to genome-wide significance of p<5x10^-8.

Question 8

Trouble with going from GWAS to biological relevance

Answer 8

1. Variants discovered are often noncoding and it is difficult to determine which coding region they interact with.
2. There are many genes in a region identified via linkage disequilibrium
3. Regions often have few connections to well established biology, making appraisal of relevancy difficult

Question 9

expression quantitative trait locus

Answer 9

When a variant is associated with gene expression

Question 10

GWAS were designed to query ____ genetic variants for associations with ____ diseases and traits

Answer 10

GWAS were designed to query common genetic variants for associations with polygenic diseases and traits,

or common variants of modest effect