Genome-wide Association Study

In genetic epidemiology, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait. GWAS typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major diseases.

These studies normally compare the DNA of two groups of participants: people with the disease (cases) and similar people without (controls). Each person gives a sample of DNA, from which millions of genetic variants are read using SNP arrays. If one type of the variant (one allele) is more frequent in people with the disease, the SNP is said to be "associated" with the disease. The associated SNPs are then considered to mark a region of the human genome which influences the risk of disease. In contrast to methods which specifically test one or a few genetic regions, the GWA studies investigate the entire genome. The approach is therefore said to be non-candidate-driven in contrast to gene-specific candidate-driven studies. GWA studies identify SNPs and other variants in DNA which are associated with a disease, but cannot on their own specify which genes are causal.

The first successful GWA study was published in 2005 and investigated patients age-related macular degeneration. It found two SNPs which had significantly altered allele frequency when comparing with healthy controls. As of 2011, hundreds or thousands of individuals are tested, over 1,200 human GWA studies have examined over 200 diseases and traits, and almost 4,000 SNP associations have been found. Several GWA studies have received criticism for omitting important quality control steps, rendering the findings invalid, but modern publications address these issues. However, the methodology itself still has opponents.