Genetics of common disease

Question 1

What are common diseases?

Answer 1

Common diseases are multifactorial

Question 2

What is sudden cardiac death?

Answer 2

Death from definite or probable cardiac causes within 1 hour of onset of problems

Question 3

What interval is highly linked with sudden cardiac death?

Answer 3

Q-T interval is highly linked with sudden cardiac death

Question 4

How is the heritability of ECG indices estimated?

Answer 4

Estimated by looking at differences in the correlation of monozygotic and dizygotic twin pairs

Question 5

What is the heritability of ECG indices scored between?

Answer 5

Scored between 0-1

Question 6

What does high heritability imply?

Answer 6

High heritability implies a strong resemblence

Question 7

What is concordance?

Answer 7

It’s how similar phenotype is

Question 8

When interpreting twin studies, what is the effect when there are more genes involved?

Answer 8

The more genes involved, the greater the difference

Question 9

What is worth doing when something is proven to be heritable?

Answer 9

Once something is proven to be heritable, it is worth doing studies to see which genes are involved

Question 10

What are SNPs?

Answer 10

They’re DNA sequence variations that occur when a single nucleotide is altered

Question 11

What are the most common form of variation in the human genome?

Answer 11

SNPs are the most common form of variation in the human genome

Question 12

What have SNPs been catalogued in?

Answer 12

Have been catalogued in several databases

Question 13

What do we do in GWAS?

Answer 13

In GWAS, we interrogate SNPs that commonly arise in the population

Question 14

What do most GWAS involve?

Answer 14

Involve comparing unaffected with the affected

Question 15

What is the short term goal of GWAS?

Answer 15

The short term goal is to identify genetic variants that explain differences in phenotype among individuals in a study population

Question 16

What can follow if in GWAS we find an association?

Answer 16

• Understanding mechanisms of action and disease etiology in individuals
• Characterize relevance and/or impact in more general population

Question 17

What is the long term goal in GWAS?

Answer 17

To inform process of identifying and delivering better prevention and treatment strategies

Question 18

What is linkage disequilibrium?

Answer 18

It’s the non random association of alleles at different loci which may or may not be due to linkage

Question 19

What happens to linkage disequilibrium with increase in physical distance?

Answer 19

In general, LD between two SNPs decrease with physical distance

Question 20

What does the extent of LD variation depend on?

Answer 20

Extent of LD varies greatly depending on region of genome

Question 21

What do we need fewer when LD is strong?

Answer 21

If LD is strong, we need fewer SNPs to capture variation in a region

Question 22

Interpreting the statistical results

Answer 22

If we set P-value threshold for each test to be 0.05, by chance we will find 5% of the SNPs to be associated with the disease

Question 23

What is the bonferroni correction?

Answer 23

If the number of tests is n, we set the threshold to be 0.05/n

Question 24

What are the 3 possibilities if you identify a SNP that is significantly associated with the disease?

Answer 24

• There is a causal relationship between SNP and disease
• The marker is in linkage disequilibrium with a causal locus
• False positives