missing heritability

Zuk O, Hechter E, Sunyaev SR & Lander ES 2012 The mystery of missing heritability: genetic interactions create phantom heritability. PNAS 109:1193-1198.

• a substantial portion of missing heritability could arise from overestimation of the denominator
• (i) estimates of total heritability implicitly assume the trait involves no genetic interactions (epistasis) among loci
• (ii) this assumption is not justified
• models with interactions are also consistent with observable data
• (iii) under such models, the total heritability may be much smaller and thus the proportion of heritability explained much larger

• human genetic studies of missing heritability have paid little attention to the potential impact of genetic interactions
• the prevailing view among human geneticists appears to be that interactions play at most a minor part in explaining missing heritability