Chunk #49 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.1 Are endophenotype effect sizes larger than those of other phenotypes?
The effects described in the previous paragraph are for associations between genetic variants and genetically distal phenotypes like BMI, height, cigarettes per day, or type II diabetes. Our own work described in the previous section, using a discovery sample of 4,900 individuals, provides little reason to expect electrophysiological endophenotypes to be any different. We found only one significant GWAS hit, yet to be replicated, for any of the 17 endophenotypes investigated. The effect size of the most significant common variant we discovered (rs1868457) accounted for 0.67% of the variance in antisaccade eye tracking errors (p=3.3×10-9, Vaidyanathan, Malone, Donnelly, et al., 2014a), and that value is undoubtedly inflated due to “winner's curse” (Ioannidis, 2008). Replication attempts will only result in attenuated effect sizes for this variant. Brain structural measures, which arguably are more proximal to gene effects than electrophysiological measures recorded from the body surface, fare no better. The ENIGMA consortium (Thompson et al., 2014) combined GWAS data across multiple samples and conducted a meta-analysis of hippocampal and intracranial volume from structural MRI in a discovery sample of 7,795 individuals and
