The pursuit of genome-wide association studies: where are we now?

Abstract

It is now 5 years since the first genome-wide association studies (GWAS), published in 2005, identified a common risk allele with large effect size for age-related macular degeneration in a small sample set. Following this exciting finding, researchers have become optimistic about the prospect of the genome-wide association approach. However, most of the risk alleles identified in the subsequent GWAS for various complex diseases are common with small effect sizes (odds ratio o1.5). So far, more than 450 GWAS have been published and the associations of greater than 2000 single nucleotide polymorphisms (SNPs) or genetic loci were reported. The aim of this review paper is to give an overview of the evolving field of GWAS, discuss the progress that has been made by GWAS and some of the interesting findings, and summarize what we have learned over the past 5 years about the genetic basis of human complex diseases. This review will focus on GWAS of SNPs association for complex diseases but not studies of copy number variations.

Gene–gene interactions contribute to eye colour variation in humans

“…9 Several genes were associated with various pigment traits long before the genome-wide association study era. [10][11][12][13][14][15][16] However, it is important to note that-unlike in the case of testing for many complex diseases 17 genome-wide association study has been particularly effective in association testing for human pigmentation and has confirmed already known, and revealed multiple new polymorphisms and loci involved in determination of human pigmentation. [18][19][20][21] This has been particularly striking in the case of variation in eye colour, which is assessed to be 50% explained by known polymorphisms.…”

Comparative oncology: what dogs and other species can teach us about humans with cancer

“…The approach of using genome-wide association studies (GWAS) in humans to identify disease-risk alleles has been relatively successful, with an explosion in published GWAS data over the past decade [33,34], although admittedly, revealing varying levels of clinically significant disease risk [35,36]. In dogs, the rewards of GWAS can be more readily realized owing to the genetic homogeneity readily found within dog breeds [15,37].…”

Sex‐specific association of a common variant of the XG gene with autism spectrum disorders

“…The functional role of these intergenic SNPs is not clear, but studies have demonstrated that non-protein-coding regions may be functional if, for example, the loci coincide with some regulatory elements for genes, either already known or yet to be characterized, involved in development or transcription [Ku et al, 2010]. Alternatively, these non-protein-coding SNPs may serve as surrogate markers that tag functional variants that are as yet unknown, since current SNP selection methods for commercial GWAS genotyping arrays are predominantly guided by LD information and not functionality [Ku et al, 2010].Intellectual disability (ID) is a common co-morbid condition in ASD-affected individuals and a similar sex difference has long been observed for ID. Although we were unable to disentangle whether the observed associations were related to ASD itself or to co-morbid ID, since IQ information was not consistently collected in the AGRE repository, the nonverbal and verbal IQ scores that were available for half of the cases included in the current sample were similar in MO and FC families, suggesting that the associations were not likely to be specific to co-morbid ID (Table I).…”