large number of rare variants as well. Ultimately, every gene contributes to every trait, but with effect sizes so small that it would take samples greater than the population size of the species to detect them. In practice, as shown by the massive meta-analyses of GWAS for height and body mass index (BMI)13,14, each involving several hundred thousand people, it is unlikely that more than a few hundred loci will ever be confirmed for most diseases, and these will not necessarily explain even half of the genetic variance. The term infinitesimal borrows from the initial formulation of quantitative genetic theory by RA Fisher7. Here it simply signifies the idea that the heritability is not so much missing, as hidden beneath the significance thresholds used to define risk alleles with high confidence15.
