We can examine the idea that a specific physiology has a “purer genetic signal”, in the sense that it has a more tractable genetic architecture, by looking at what is known about the genetic basis of physiological phenotypes far simpler than psychiatric disease. It seems reasonable to propose that measures of protein concentration and metabolites levels qualify as probes for more specific physiology; in other words, they should be good intermediate phenotypes. The locus-specific effects of such phenotypes are all small: the mean effect size for 95 loci that influence blood lipids is 0.12% phenotypic variance [37], while the 17 loci so far discovered that contribute to variation in serum C-reactive protein have a mean effect size of 0.28% [38]. The 26 loci influencing serum urate levels have a mean effect size of 0.26% of phenotypic variance [39]. Effect sizes on cellular phenotypes are of a similar magnitude — 0.12% of phenotypic variance for 75 loci contributing to variation in mean red cell volume [40].
