Genetics of common disease Flashcards
What are common diseases?
Common diseases are multifactorial
What is sudden cardiac death?
Death from definite or probable cardiac causes within 1 hour of onset of problems
What interval is highly linked with sudden cardiac death?
Q-T interval is highly linked with sudden cardiac death
How is the heritability of ECG indices estimated?
Estimated by looking at differences in the correlation of monozygotic and dizygotic twin pairs
What is the heritability of ECG indices scored between?
Scored between 0-1
What does high heritability imply?
High heritability implies a strong resemblence
What is concordance?
It’s how similar phenotype is
When interpreting twin studies, what is the effect when there are more genes involved?
The more genes involved, the greater the difference
What is worth doing when something is proven to be heritable?
Once something is proven to be heritable, it is worth doing studies to see which genes are involved
What are SNPs?
They’re DNA sequence variations that occur when a single nucleotide is altered
What are the most common form of variation in the human genome?
SNPs are the most common form of variation in the human genome
What have SNPs been catalogued in?
Have been catalogued in several databases
What do we do in GWAS?
In GWAS, we interrogate SNPs that commonly arise in the population
What do most GWAS involve?
Involve comparing unaffected with the affected
What is the short term goal of GWAS?
The short term goal is to identify genetic variants that explain differences in phenotype among individuals in a study population
What can follow if in GWAS we find an association?
- Understanding mechanisms of action and disease etiology in individuals
- Characterize relevance and/or impact in more general population
What is the long term goal in GWAS?
To inform process of identifying and delivering better prevention and treatment strategies
What is linkage disequilibrium?
It’s the non random association of alleles at different loci which may or may not be due to linkage
What happens to linkage disequilibrium with increase in physical distance?
In general, LD between two SNPs decrease with physical distance
What does the extent of LD variation depend on?
Extent of LD varies greatly depending on region of genome
What do we need fewer when LD is strong?
If LD is strong, we need fewer SNPs to capture variation in a region
Interpreting the statistical results
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
What is the bonferroni correction?
If the number of tests is n, we set the threshold to be 0.05/n
What are the 3 possibilities if you identify a SNP that is significantly associated with the disease?
- There is a causal relationship between SNP and disease
- The marker is in linkage disequilibrium with a causal locus
- False positives
