What is a genome-wide association study (GWAS)?

In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.

When applied to human data, GWA studies compare the DNA of participants having varying phenotypes for a particular trait or disease. These participants may be people with a disease (cases) and similar people without the disease (controls), or they may be people with different phenotypes for a particular trait, for example blood pressure. This approach is known as phenotype-first, in which the participants are classified first by their clinical manifestation(s), as opposed to genotype-first. Each person gives a sample of DNA, from which millions of genetic variants are read using SNP arrays. If there is significant statistical evidence that one type of the variant (one allele) is more frequent in people with the disease, the variant is said to be associated with the disease. The associated SNPs are then considered to mark a region of the human genome that may influence the risk of disease.

GWA studies investigate the entire genome, in contrast to methods that specifically test a small number of pre-specified genetic regions. Hence, GWAS is a non-candidate-driven approach, in contrast to gene-specific candidate-driven studies. GWA studies identify SNPs and other variants in DNA associated with a disease, but they cannot on their own specify which genes are causal.

The first successful GWAS published in 2002 studied myocardial infarction. This study design was then implemented in the landmark GWA 2005 study investigating patients with age-related macular degeneration, and found two SNPs with significantly altered allele frequency compared to healthy controls. As of 2017, over 3,000 human GWA studies have examined over 1,800 diseases and traits, and thousands of SNP associations have been found. Except in the case of rare genetic diseases, these associations are very weak, but while they may not explain much of the risk, they provide insight into genes and pathways that can be important.