Results
Attempts have been made at creating comprehensive catalogues of SNPs that have been identified from GWA studies. As of 2009, SNPs associated with diseases are numbered in the thousands.
The first GWA study, conducted in 2005, compared 96 patients with age-related macular degeneration (ARMD) with 50 healthy controls. It identified two SNPs with significantly altered allele frequency between the two groups. These SNPs were located in the gene encoding complement factor H, which was an unexpected finding in the research of ARMD. The findings from these first GWA studies have subsequently prompted further functional research towards therapeutical manipulation of the complement system in ARMD. Another landmark publication in the history of GWA studies was the Wellcome Trust Case Control Consortium (WTCCC) study, the largest GWA study ever conducted at the time of its publication in 2007. The WTCCC included 14,000 cases of seven common diseases (~2,000 individuals for each of coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn's disease, bipolar disorder, and hypertension) and 3,000 shared controls. This study was successful in uncovering many new disease genes underlying these diseases.
Since these first landmark GWA studies, there have been two general trends. One has been towards larger and larger sample sizes. At the end of 2011, the largest sample sizes were in the range of 200,000 individuals. The reason is the drive towards reliably detecting risk-SNPs that have smaller odds ratios and lower allele frequency. Another trend has been towards the use of more narrowly defined phenotypes, such as blood lipids, proinsulin or similar biomarkers. These are termed intermediate phenotypes and their analyses are suggested to be of value to functional research into biomarkers.
A central point of debate on GWA studies has been that most of the SNP variations found by GWA studies are associated with only a small increased risk of the disease, and have only a small predictive value. The median odds ratio is 1.33 per risk-SNP, with only a few showing odds ratios above 3.0. These magnitudes are considered small because they do not explain much of the heritable variation. This heritable variation is known from heritability studies based on monozygotic twins. For example it is known that 80–90% of height is heritable. This means that if 29 cm separates the tallest 5% from the shortest 5% of the population, then genetics account for 27 cm. Of these 27 cm, however, the GWA studies only account for a minority. In the height example it is 6 cm, and for most other major complex phenotypes it is a similar small fraction.
Read more about this topic: Genome-wide Association Study
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