Genome-wide association study

A GWAS tests hundreds of thousands to millions of genetic markers, usually single nucleotide polymorphisms (SNPs), spread across the whole genome of a large group of people. In the classic design, researchers compare people who have a disease (cases) with similar people who do not (controls), reading each person's DNA, often from blood or a cheek swab, on a genotyping chip. A variant that turns up clearly more often in one group is said to be associated with the disease. The same approach works for measured traits such as height.

Because so many variants are tested at once, GWAS use very strict statistical thresholds to avoid false positives. An association points to a region of the genome, not necessarily the cause: the flagged SNP may simply be inherited along with a nearby causal variant, so follow-up sequencing and lab work are needed. Most associated variants raise risk only slightly, but many together can be combined into a polygenic risk score.

The first GWAS was published in 2005, linking age-related macular degeneration to the complement factor H gene. Results are now collected in the NHGRI-EBI GWAS Catalog.