Another overall finding from the first era of GWAS is that the heritability explained by SNP associations is significantly less than estimates of heritability derived from family studies. More specifically, the variants that reach statistical significance typically explain only a small fraction of the heritability. This is commonly referred to as the “missing heritability” problem (Manolio et al., 2009). There have been several explanations presented to explain the missing heritability, some of which include: undetected rare variants of large effect, epistatic interactions, and the idea that heritability estimates from family studies may actually be overinflated (Golan et al., 2014; Munoz et al., 2016; Zuk et al., 2012, 2014).
