Chunk #48 — 6.0 How Do Electrophysiological Endophenotypes Compare with Other Quantitative Traits? — 6.1 Are endophenotype effect sizes larger than those of other phenotypes?
(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 variants associated with Type II diabetes from a recent publication was 1.11 (Morris et al., 2012). The average effect of the nearly 700 GWAS-associated variants with height, one of the most accurately measured and highly heritable of all human quantitative traits, is around r2=0.03% (Wood et al., 2014). The SNP rs16969968 in CHRNA5 accounts for 0.5% of the variance in cigarettes per day (Furberg et al., 2010), one of the largest effects discovered between a common variant and a complex behavioral or psychiatric phenotype. Not only is r2=0.5% a very large effect, it is about the largest effect one now expects to find in a genetic association study of complex traits and common variants. Detecting effects of these sizes requires massively powered studies on a scale that until recently was not achieved in biomedical or behavioral science.
