Association analysis Flashcards
What is genetic association?
Genetic association is the presence of a variant allele at a higher frequency in unreliable subjects with a particular disease, compared to those that do not have the disease
What is an allele?
One form of a varient in the genome
What is a locus?
A position in the genome
What is a genotype?
Both alleles at a locus
What is a haplotype?
It is the order of alleles along a chromosome
What are cases?
Cases are subjects with the disease of interest
What do case control association search for?
Search for variant in cases and control
Refer to diagram in notes as well or PPT to those using my flashcards
What do the best case control genetic studies have?
Have:
- Large number of well designed cases
- Equal numbers of matched controls
- Reliable genotyping technology(SNP array)
- Standard statistical analysis(PLINK)
- Positive results must be replicated
What are ideal characteristics of genetic markers?
- Polymorphic
- Randomly distributed across the genome
- Fixed location in genome
- Frequent in genome
- Frequent in population
- Stable with time
- Easy to assay
What is dbSNPs?
Database of SNPs
What are on the either sides of SNPs?
There’re unique flanking sequences on either side of the SNP
What is the rs number?
The rs number is a unique identifier given to each SNP
What is the less common allele referred to as?
Referred to as the minor allele
What do GWAS use and give an example?
Use markers across the whole genome
What are we usually looking for in GWAS and what test can we use to statistically confirm a link?
Looking for an association between the disease and each marker
-Chi-squared test
In what way is GWAS data presented as?
Presented as a single graph called a manhattan plot
What do the x and y axis in a GWAS results plot represent?
x axis- Position of the SNP on the chromosome
y axis- (-log(P-value)) of the association
In GWAS results, what does the peak identify and not identify?
Identifies genomic region associated with the disease
Does not identify the gene causing the disease
What does meta analysis allow and why is it easier?
Allows the statistical combination of results from multiple studies
-Easier to combine smaller studies than having to do large studies
What are the problems with GWAS?
- GWAS has identified associations that are statistically strong and reproductive
- However contribution to the genetic component of disease is estimated to be low due to:
- Epigenetic variation
- Heritability is overestimated
- Common SNPs of small effect
- Rare SNPs
- Copy number variation
