The combined effect of SNP-marker and phenotype attributes in genome-wide association studies

The last decade has seen rapid improvements in high-throughput single nucleotide polymorphism (SNP) genotyping technologies that have consequently made genome-wide association studies (GWAS) possible. With tens to hundreds of thousands of SNP markers being tested simultaneously in GWAS, it is imperative to appropriately pre-process, or filter out, those SNPs that may lead to false associations. This paper explores the relationships between various SNP genotype and phenotype attributes and their effects on false associations. We show that (i) uniformly distributed ordinal data as well as binary data are more easily influenced, though not necessarily negatively, by differences in various SNP attributes compared with normally distributed data; (ii) filtering SNPs on minor allele frequency (MAF) and extent of Hardy–Weinberg equilibrium (HWE) deviation has little effect on the overall false positive rate; (iii) in some cases, filtering on MAF only serves to exclude SNPs from the analysis without reduction of the overall proportion of false associations; and (iv) HWE, MAF and heterozygosity are all dependent on minor genotype frequency, a newly proposed measure for genotype integrity.