Empirical observation suggests that much of the missing heritability is contributed by causal variants (including loci comprising multiple rare variants) having effect size too small to be detected with stringent statistical significance [6],[12],[18]. Larger samples for GWAS are needed to detect these which would directly compete with research funds used in sequencing studies. Our assessment is that that the importance of synthetic associations generated by multiple variants has been overstated. Sample sizes of about 50,000 cases and 50,000 controls are required for a GWAS of schizophrenia [7] to afford the same power in detection of variance explained as a GWAS of 180,000 individuals for height [6]. The height study found that in 13 of 21 loci containing a known skeletal growth gene, the known gene was closest to the most associated variant in the region, leading the authors to make the general conclusion that the likely causal gene is often located near the most strongly associated variant [6]. Genes identified through GWAS harbouring common variants are likely to be good targets for identification of rare variants and for sorting the
