Abstract
Several studies involving genome-wide scans of non-synonymous SNPs (nsSNPs) have successfully identified loci contributing to common complex diseases. We were interested in the extent to which these small scans involving a few thousand non-synonymous markers might complement the results from denser genome-wide association studies. We assessed the degree to which three commercially available genome-wide marker panels tagged nsSNPs on the Illumina HumanNS-12 BeadChip, a product specifically designed to capture non-synonymous variation. We demonstrate that commercially available genome-wide panels already tag the majority of common non-synonymous variants on the NS-12 BeadChip, indicating that with respect to capturing common non-synonymous variation, information from the NS-12 BeadChip is largely redundant. In contrast, genome-wide panels fail to capture most of the rare SNPs present on the NS-12 BeadChip. Power calculations reveal that non-synonymous scans involving sample sizes typical of the current wave of genome-wide association studies are unlikely to identify rare variants of small effect, but could conceivably identify rare variants of intermediate penetrance. We conclude that non-synonymous scans may facilitate the identification of rare variants of intermediate penetrance that would not otherwise be detectable using dense genome-wide panels, but are unlikely to uniquely identify common variants contributing to complex disease variation.
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Acknowledgements
This work was supported by the Wellcome Trust and the National Institutes of Health (EY-126562 to LRC).
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The URL for data presented herein is as follows: the International HapMap website (http://www.hapmap.org/genotypes/latest/fwd_strand/non-redundant/).
Supplementary Information accompanies the paper on European Journal of Human Genetics website (http://www.nature.com/ejhg)
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Evans, D., Barrett, J. & Cardon, L. To what extent do scans of non-synonymous SNPs complement denser genome-wide association studies?. Eur J Hum Genet 16, 718–723 (2008). https://doi.org/10.1038/sj.ejhg.5202011
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DOI: https://doi.org/10.1038/sj.ejhg.5202011
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