Genome-wide Association Study - Background

Background

Any two human genomes differ in millions of different ways. There are small variations in the individual nucleotides of the genomes (SNPs) as well as many larger variations, such as deletions, insertions and copy number variations. Any of these may cause alterations in an individual's traits, or phenotype, which can be anything from disease risk to physical properties such as height. Around the year 2000, prior to the introduction of GWA studies, the primary method of investigation was through inheritance studies of genetic linkage in families. This approach had proven highly useful towards single gene disorders. However, for common and complex diseases the results of genetic linkage studies proved hard to reproduce. A suggested alternative to linkage studies was the genetic association study. This study type asks if the allele of a genetic variant is found more often than expected in individuals with the phenotype of interest (e.g. with the disease being studied). Early calculations on statistical power indicated that this approach could be better than linkage studies at detecting weak genetic effects.

In addition to the conceptual framework several additional factors enabled the GWA studies. One was the advent of biobanks, which are repositories of human genetic material which greatly reduced the cost and difficulty of collecting sufficient numbers of biological specimens for study. Another was the International HapMap Project which from 2003 had identified a majority of the common SNPs which are interrogated in a GWA study. The haploblock structure identified by HapMap project also allowed the focus on the subset of SNPs that would describe most of the variation. Also the development of the methods to genotype all these SNPs using genotyping arrays was an important prerequisite.