Tests of association based on genomic windows can lead to spurious associations when using genotype panels with heterogeneous SNP densities

Abstract

Dense single nucleotide polymorphism (SNP) panels are widely used for genome-wide association studies (GWAS). In these panels, SNPs within a genomic segment tend to be highly correlated. Thus, association studies based on testing the significance of single SNPs are not very effective, and genomic-window based tests have been proposed to address this problem. However, when the SNP density on the genotype panel is not homogeneous, genomic-window based tests can lead to the detection of spurious associations by declaring effects of genomic windows that explain a large proportion of genetic variance as significant. We propose two methods to solve this problem.