Chunk #54 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.1 Are endophenotype effect sizes larger than those of other phenotypes?
From this snapshot of the GWAS literature, the distribution of effects for the more “biological” blood-derived phenotypes are not of materially greater magnitude as those observed for highly complex and distal phenotypes, including height and BMI. A few trends stand out. First, whereas some of the biomarkers tend to have much larger maximum effect sizes (~2% for serum urate and cotinine, 1.2% for cholesterol, 0.5% for bone marrow density), the largest effect sizes for the brain-based and heart rate endophenotypes are actually smaller than those observed for height and BMI. Second, the largest effect sizes observed for education levels and neuroticism were an order of magnitude smaller than the largest effect sizes for the brain-based and heart rate endophenotypes. Thus, endophenotypes may be associated with slightly larger effect sizes than distal psychological traits (like neuroticism), but these effects are still so small that massive sample sizes are still required to detect them (see discussion of power in section 7.3 below). Third, the most direct comparison available in Figure 1 is that between cigarettes per day and cotinine, the primary metabolite
