Chunk #58 — 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?
We can use GREML-derived estimates of SNP heritability to ask whether common variants are likely to account for a greater proportion of variance in endophenotypes than clinical phenotypes or other complex phenotypes, which might in turn increase the likelihood of gene discovery. This might be the case if endophenotypes, by virtue of reflecting relatively fundamental psychological and neurobiological processes, are influenced primarily by common variants but psychiatric disorders are disproportionately influenced by mutations and rare variants (Singh et al., 2016). To address this, we draw again on results from our recent special issue of Psychophysiology that are provided in Table 2. Excluding startle modulation scores, which showed little evidence of being heritable (95% confidence intervals around our family-based heritabilities included 0), the ratio of SNP heritability to family-based heritability ranged widely, with a median of 0.54. This is almost exactly equal to the SNP heritability to biometric heritability ratio for height, which is 0.56 if we assume a heritability estimate of 0.8 for height. What these estimates rather convincingly demonstrate is that endophenotypes are far from immune to the missing heritability problem, and they do not differ from other phenotypes with respect to their overall genetic architecture.
