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Review
. 2012 Jan 13;90(1):7-24.
doi: 10.1016/j.ajhg.2011.11.029.

Five years of GWAS discovery

Peter M Visscher  1 , Matthew A Brown, Mark I McCarthy, Jian Yang
Affiliations
Review

Five years of GWAS discovery

Peter M Visscher et al. Am J Hum Genet. .

Abstract

The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section.

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Figures

Figure 1
Figure 1
GWAS Discoveries over Time Data obtained from the Published GWAS Catalog (see Web Resources). Only the top SNPs representing loci with association p values < 5 × 10−8 are included, and so that multiple counting is avoided, SNPs identified for the same traits with LD r2 > 0.8 estimated from the entire HapMap samples are excluded.
Figure 2
Figure 2
Increase in Number of Loci Identified as a Function of Experimental Sample Size (A) Selected quantitative traits. (B) Selected diseases. The coordinates are on the log scale. The complex traits were selected with the criteria that there were at least three GWAS papers published on each in journals with a 2010–2011 journal impact factor >9 (e.g., Nature, Nature Genetics, the American Journal of Human Genetics, and PLoS Genetics) and that at least one paper contained more than ten genome-wide significant loci. These traits are a representative selection among all complex traits that fulfilled these criteria.
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