A genome-wide association study (GWAS) is a study method in genomics. The method is a form of observational study where you go through gene variants in several individuals to see which ones are linked to a certain phenotype. The purpose of the studies is usually to show a correlation between single-base polymorphisms (SNP for Single Nucleotide Polymorphy) and the incidence of disease in humans. However, the method can be applied to any organism and can study any phenotype that is regulated via gene expression, not just diseases. Whole genome studies examine the entire genome, in contrast to various other methods that specifically test a small number of predetermined genetic regions. Whole genome studies are therefore not dependent on identifying and selecting a number of candidate genes to study in advance.
In human medicine, whole-genome studies compare the genome of study participants with different phenotypes for a certain trait, usually a disease. These participants are then divided into different groups where one group is affected (cases) and the other is healthy (controls). Each person provides a sample of DNA, from which millions of genetic variants are read with SNP matrices. If a gene variant is more common in people with the disease, the variant is said to be associated with the disease. Complete genome studies alone cannot prove causation. The first successful GWAS was published in 2002 and studied myocardial infarction. The study design was reused in 2005 in a study of age-related macular degeneration where two SNPs with significantly changed gene frequency could be identified compared to healthy controls. In 2017, over 3,000 holistic studies had been conducted on people with a total of over 1,800 diseases or other characteristics examined and identified thousands of associated SNPs as a result.
Two randomly selected human genomes differ by several million base pairs. There are variations in the individual nucleotides in the genome (SNP) as well as larger differences on several base pairs in a row. Both of these can cause changes in a person's characteristics, such as disease risk or physical characteristics such as height. Around the year 2000, before the introduction of GWA studies, the primary research method was through genetic studies of genetic linkage in families. This approach had proven to be very useful against occasional genetic disorders. However, for common and complex diseases, the results of genetic linkage studies proved difficult to reproduce. A proposed alternative to linkage studies was the genetic association study. This type of study asks whether the allele of a genetic variant is found more often than expected in individuals with the phenotype of interest (eg with the disease being studied). Early calculations of statistical effect indicated that this approach could be better than linkage studies to detect weak genetic effects. Several factors facilitated the implementation of the first whole genome studies. One was the creation of biobanks, which facilitated the collection of the large amounts of sample material required to conduct the studies. Another was the International HapMap Project, which helped identify the majority of the SNPs examined in holistic studies. Most holistic studies are designed as case-control studies. Two large groups of individuals are compared with each other, a healthy control group and a fall group are affected by a certain disease. All individuals in the groups are genotyped for most common and known SNPs. The exact number of SNPs depends on the method of genotyping, but is usually one million and up. For each of these SNPs, it is then examined whether the allele frequency changes significantly between the fall group and the control group. The effect size between the different groups is represented as an odds ratio.
Attempts have been made to create catalogs of SNPs that have been identified in holistic studies. As early as 2009, there were thousands of well-known SNPs who connect