Lecture 5: Genomics and Health Part 2 Flashcards
What do Genome-Wide Association Studies do?
SNP arrays are used to genotype individuals with and without a particular disease trait
If there is a higher incidence of a SNP allele in individuals with the trait compared to those without, this is referred to as association
The significance of the association depends on the degree of association and sample size (Larger sample size = more confidence in P value for association)
What is different about the P value used to test for association with any SNP?
the P value is extremely stringent to identify true association and avoid false positives
(Typically GWAS uses a threshold P value of 5x10^-8)
What does a stringent P value mean for the sample size requirement?
Needs to be large
Haplotypes within a block exhibit a high level of what?
Linkage disequilibrium (low rate of random recombination) meaning that certain haplotypes (SNP allele combinations) are more frequent than others
What are tag SNPs and why are they used?
SNPs that is used to represent all the SNPs in a particular haplotype block (in linkage disequilibrium so can predict the alleles present at the other SNP locations within the block). These tag SNPs are sequenced to remove the need to sequence every single SNP in a particular haplotype block.
If a tag SNP is in the same haplotype block as a disease SNP, the genotype of the tag SNP should allow you to determine the likely genotype of the disease SNP as they are linked.
How are tag SNPs used in GWAS?
GWAS study a range of tag SNPs to identify any associated with a disease SNP in order to determine which individuals have a genetic predisposition to a disease
From the found associated tag SNPs following GWAS, how can the lead SNP of a haplotype block be identified and what is a lead SNP?
The tag SNPs identified to be associated with the disease SNP undergo linkage disequilibrium clumping methods to computationally determine the lead SNP
The lead SNP is the SNP with the smallest/most significant P value for association
What type of plot is used to visualise the p-values for investigated SNPs across the genome locations in GWAS?
Manhattan plot
(the chromosomes are on the X-axis and often colour coded to distinguish between them
the association between the genotyped SNP and a disease SNP = more significant association = higher up the Y-axis (-log10(P))
True or False: GWAS only shows
What can DNA or RNA profiling be used to inform?
Precision medicine (identifying diagnosis or appropriate treatments, pharmacogenetics)
What is pharmacogenetics?
determining how genetics influences drug response
