1. ¹Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
2. ²MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, UK

Correspondence: Dr DM Evans, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK. Tel: +44 (0)117 9287200; Fax: +44 (0)117 9287292; E-mail: dave.evans@bristol.ac.uk

Received 13 September 2007; Revised 10 December 2007; Accepted 20 December 2007; Published online 16 January 2008.

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.