Chunk #55 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.1 Are endophenotype effect sizes larger than those of other phenotypes?
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 of nicotine and long a biomarker for nicotine consumption and addiction (Benowitz, 1996). The maximum effect sizes for both traits is from the same variant, rs16969968. The variant accounts for ~0.4% of the variation in cigarettes per day but 1.8% in cotinine, clearly a larger effect on the biomarker than the behavioral phenotype. Cotinine is not an endophenotype, however, and to our knowledge stands alone as a successful biomarker for a psychiatric condition, in this case nicotine addiction, largely thanks to our advanced understanding of nicotine pharmacokinetics. Fourth, the largest effect sizes for the blood-derived biomarkers listed here are 2-3x larger than those for physical traits, an order of magnitude larger than the brain volume measures, and many times larger than those for more psychological phenotypes. However, this applies only to the 1-2 largest effects. The vast majority of observed effects for all traits, whether blood-derived biomarker or years of education, is well below r2=0.1%.
