Launched in 2002, the International HapMap Project was a collaborative effort among scientists from around the world to create a map of common patterns of genetic variation in the human genome. HapMap stands for haplotype map. A haplotype is a stretch of DNA nucleotides, or letters, that individuals inherit as a block because they lie relatively close together along a chromosome. For any particular region of a chromosome, there may be multiple different haplotypes present among humans, each characterized by a slightly different DNA sequence. By collecting and analyzing the DNA of initially 270 individuals from several different geographic regions, HapMap scientists were able to identify common haplotypes that exist among those individuals, as well as reliable markers to distinguish them. That collection of haplotypes and identifying markers—the HapMap—provided a shortcut for researchers who wanted to identify associations between those inherited DNA variants and particular human traits, especially common, complex diseases like heart disease and cancer.

A genome-wide association study, or GWAS, is a method for identifying variations in DNA that may contribute to the development of a particular trait, such as a disease. A GWAS relies on identifying statistical correlations between many, often thousands of, DNA markers and a particular trait. Scientists employ GWASs to try to identify the genetic contributions to complex traits, such as common human diseases. Complex traits are ones that scientists suspect are the result of multiple genes and environmental inputs acting together, in contrast to simple, Mendelian disorders that result primarily from the disturbance of a single gene. The genetic variants identified through a GWAS typically account for only a small proportion of the expected genetic contribution to a complex trait, which scientists refer to as the missing heritability problem. Since 2006, scientists have conducted thousands of GWASs aimed at identifying the genetic contributions to complex traits and have identified many thousands of genetic variations that correlate with those traits, although as of 2025, because of the missing heritability problem and other limitations, the concrete contributions of GWASs to medicine have so far been modest.

In 1998, Francis Collins, then director of the US National Human Genome Research Institute, or NHGRI, announced the creation of a tool for discovering genetic variation called the DNA Polymorphism Discovery Resource, or PDR. The PDR was a collection of cell lines housed in a central biobank. Scientists made those cell lines from blood samples they obtained from 450 US residents of diverse ancestry. They created the PDR to help researchers discover a particular type of genetic variation called single nucleotide polymorphisms, or SNPs. A SNP is a variation in a single letter of DNA at a particular location along a DNA molecule. SNPs can serve as markers when scientists look for associations between specific DNA regions and human traits, including common diseases like heart disease and cancer. Although as of 2024 the PDR is no longer available, it enabled scientists to identify more than a million SNPs spread over the whole human genome, a necessary precursor to studies aimed at identifying genetic variation that contributes to health and illness.