p1 Benefits
Genome- wide association studies (GWAS) involve testing genetic variants across
the genomes of many individuals to identify genotype–phenotype associations.
led to insights into the architecture of
disease susceptibility
GWAS have revolutionized the field of complex disease genetics over the past decade, providing numerous compelling associations for human complex traits and diseases.
to advances in clinical care and personalized medicine
GWAS has been very successful in identifying novel variant–trait associations.
GWAS findings have diverse clinical applications.
GWAS can lead to the discovery of novel biological
mechanisms.
GWAS can provide insight into the ethnic variation of complex traits.
GWAS can be used to identify novel monogenic and oligogenic disease genes.
aim and steps
detect associations between allele or genotype frequency and trait status
identifying the disease or trait and selecting an appropriate study population
Genotyping can be performed using single-nucleotide polymorphism (SNP) arrays combined with imputation or whole- genome sequencing (WGS).
Causal variants are usually not directly genotyped but are in linkage disequilibrium with the genotyped SNPs.
Association tests are used to identify regions of the genome associated with the phenotype of interest at genome-wide significance
meta-analysis is a common step to increase the statistical power to detect associations.
target genes are examined
chromosome conformation capture methods
experimentally validated using cell- based systems and model organisms
chromatin immunoprecipitation
Genetic variants
Rare variants with small effect sizes are difficult to identify using GWAS
common variants with large effects are unusual for common complex diseases
Most risk variants identified by GWAS lie within the two diagonal lines