What is Genome-wide association?

A single-nucleotide polymorphism (SNP) is a position at which two bases each occur in at least $1\,\%$ of a population; about ten million are common in humans. A genome-wide association study (GWAS) genotypes hundreds of thousands of SNPs in thousands of people with a disease and thousands without, and asks at each SNP whether one allele is more frequent in the cases. Because a million tests are made, a result counts only below a significance threshold of about $5\times 10^{-8}$ ($0.05$ divided by the million effectively independent tests). Associated SNPs mark a region, not a causal variant, since neighbouring alleles travel together (linkage disequilibrium) over tens of kilobases. For most common diseases the associated alleles each shift risk by a few percent and lie mostly in regulatory sequence; their combined effect, summed over thousands of SNPs as a polygenic score, explains a fraction of the heritability and predicts risk about as well as family history.