If a genetic variant is associated with fitness, selection will drive one allele to low frequency19–21. This is the case even for traits without an obvious connection to fitness. The larger the effect of a SNP on a fitness the lower the frequencies of the causal alleles are expected to be22, 23. For example, individual mutations causing severe intellectual disability in humans are rare24, 25. Therefore, in practice, the SNPs identified as associated in the discovery population are unlikely to explain all genetic variation (i.e, hM2 < h2) since contributions to the variance by rare variants may not be tagged by the genotyped SNPs26–28. For example, for both height and schizophrenia h2 ~ 0.7–0.8 and hM2 ~ 0.5 for height26 and 0.2–0.3 for schizophrenia29, 30.
