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An Expanded View of Complex Traits: From Polygenic to Omnigenic: Cell

This debate was resolved in a seminal 1918 paper by R.A. Fisher, who showed that, if many genes affect a trait, then the random sampling of alleles at each gene produces a continuous, normally distributed phenotype in the population (Fisher, 1918). As the number of genes grows very large, the contribution of each gene becomes correspondingly smaller, leading in the limit to Fisher’s famous “infinitesimal model” (Barton et al., 2016).