genome-wide association study
Meaning of genome-wide association study: A statistical trawl across all the chromosomes at once, finding where common variation tracks with a disease without being told where to look.
Definition of genome-wide association study
A genome-wide association study compares hundreds of thousands of common DNA variants across the genomes of people with a condition against the same positions in people without it, hunting for versions that turn up more often in one group. It surveys the whole genome rather than a gene chosen in advance. The output is a list of chromosome positions statistically linked to the condition.
How does the study work?
Two large groups are assembled, one with the condition and one without, and a chip reads many thousands of positions across each person's genome where the letters of DNA commonly differ between people. Each position is then tested on its own: is one version more frequent among those affected? Because so many positions are tested at once, some will look striking by luck alone, so the bar for calling a signal real is set far higher than in an ordinary study and a finding counts only once it repeats in a separate group.
What does a hit actually tell?
Less than the phrasing suggests. A hit marks a neighborhood of a chromosome, not a gene, because nearby variants travel together in blocks and any one of them may be the tag rather than the cause. Most signals land outside the stretches that code for protein, in regions that switch genes on and off, sometimes acting on a gene lying some distance away. Working out which gene is affected, and in which tissue, is a separate project. Individual effects are also small, which is why these studies need very large numbers to see anything at all.
How does it differ from other genetic studies?
| Approach | What it examines | What it finds |
|---|---|---|
| Genome-wide association study | Common variants across every chromosome | Small effects on common disease |
| Candidate gene study | One gene picked in advance | Only an answer to the question asked |
| Linkage study in families | Inheritance patterns within a family | Rare variants with large effects |
| Whole genome sequencing | Every letter, common and rare | Rare variants a chip cannot see |
The same design is sometimes labeled a whole genome association study. One limit follows from the method rather than the technology: results hold for the population sampled, and much of the data gathered so far has come from people of European ancestry, so risk scores built on it transfer poorly to everyone else.
Also known as
Used in a sentence
The variant was first reported in a genome-wide association study of inflammatory bowel disease.
Good to know
A genome-wide association study identifies a chromosome region statistically linked to a condition rather than a causal gene, and most signals fall outside protein-coding sequence, so naming the gene responsible requires separate work.