Chunk #47 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.1 Are endophenotype effect sizes larger than those of other phenotypes?
What constitutes a powerful study in genetic research is different than in many fields. For example, in the behavioral sciences a correlation of 0.1 is considered small, 0.3 medium, and 0.5 large (Cohen, 1988). On the r2 metric (variance accounted for) these correspond to r2 of 1%, 9%, and 25%. Consider by way of contrast SNPs located in the first intron of the FTO gene, which are well known to have effects on the common complex trait of body mass index (BMI) (Locke et al., 2015). This locus was the first associated with obesity through GWAS, and a PubMed search for “FTO and obesity” revealed 868 publications at the time of this writing. The effect size of the most strongly associated variants within this locus is 0.34% on the r2 metric in Europeans and even smaller in other ancestry groups (Loos & Yeo, 2014). The FTO variant effect is large by the standards of complex disease/trait genetic association standards but is tiny, ignorable even, by behavioral science standards. BMI is not unique in this respect. The average odds ratio of
