Chunk #56 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.2 Is the “genetic architecture” of endophenotypes different from that of other phenotypes?
The GREML approach alluded to earlier is very different from GWAS, in that it estimates the aggregate effect of all measured variants (and those in linkage disequilibrium with them) rather than estimating the effect of each individual variant in turn. Although GREML cannot therefore identify the specific variants influencing a trait, it can nevertheless establish the overall magnitude of genetic variance in the trait due to the tagging SNPs on GWAS arrays, which are predominantly common variants (those with MAFs of at least 1%). The initial study using this approach examined the SNP heritability of height, one of the most heritable human traits based on twin and family studies, with heritability estimates from those studies converging on ~80% (Yang et al., 2010). GREML analysis indicated that the SNP heritability of height was 45%. Although well short of the total heritability of 80% from twin and family studies, this was also much greater than the amount of variance in height accounted for by GWAS of tens of thousands of subjects, which at the time of this 2010 publication had identified approximately
