To explore the economic ramifications of sequencing-based GWAS, we considered the trade-off between the number of samples sequenced and the average coverage (which affects accuracy). We evaluated the expected effective sample size attained with different strategies and compared this with the effective sample size that would be obtained by genotyping using standard genotyping arrays (e.g. Illumina Human-1M-duo). We derived all results from empirical accuracies using sequencing data sets sub-sampled from the IHCS data, so that results do not rely on any simulation assumptions. We compared accuracies only at SNPs typed on the array, a conservative computation that ignores the potentially greater benefit at SNPs not present on the array. We assumed a fixed total budget of $300,000, an arbitrarily large number of samples available, a sample preparation cost of $30 (conservatively double the cost that we have recently demonstrated11), and DNA sequencing cost of $133 per 1x sequencing (based on the Illumina Network cost of $4,000 for 30x sequencing of 50 samples or more, which scales linearly with lower coverage). We calculated the effective sample size of a sequencing-based GWAS
